Antiinfective 1,2,3-triazole derivatives, process for their preparation and pharmaceutical compositions containing them

ABSTRACT

The present invention relates to novel triazole compounds of formula (I), thie pharmaceutically acceptable salts and their pharmaceutical compositions, where all symbols have meaning as defined in the description, for use in the treatment of bacterial infections.

FIELD OF THE INVENTION

The present invention relates to novel triazole compounds of formula(I),

where R¹ represents halogen, azido, thioalcohol, isothiocyanate,hydroxy, isoindole-1,3-dione, substituted or unsubstituted(C1-C20)alkylsulfonyloxy, arylsulfonyloxy, (C1-C20)acyloxy group, NHR⁴where R⁴ represents hydrogen, substituted or unsubstituted groupsselected from (C1-C20)acyl, thio(C1-C20)acyl, (C1-C20)alkoxycarbonyl,(C3-C20)cycloalkoxycarbonyl, (C3-C20)cycloalkoxythiocarbonyl,(C2-C20)alkenyloxycarbonyl, (C2-C20)alkenylcarbonyl, heteroaryl,aryloxycarbonyl, heteroarylcarbonyl, heteroarylthiocarbonyl,(C1-C20)alkoxythiocarbonyl, (C2-C20)alkenyloxythiocarbonyl,aryloxythiocarbonyl, —C(═O)—C(═O)—(C1-C20)alkyl, —C(═O)—C(═O)-aryl,—C(═O)—C(═O)—(C1-C20)alkoxy, —C(═O)—C(═O)—aryloxy,—C(═O)—C(═S)—(C1-C20)alkyl, —C(═O)—C(═S)-aryl, —C(═S)—S—(C1-C20)alkyl,—C(═S)—NH₂, —C(═S)—NH—(C1-C20)alkyl, —C(═S)—N—((C1-C20)alkyl)₂,—C(═S)—NH—(C2-C20)alkenyl, —C(═S)—C(═O)—(C1-C20)alkoxy,—C(═S)—C(═O)-aryloxy, —C(═S)—O—C(═O)—(C1-C20)alkyl,—C(═S)—C(═S)—(C1-C20)alkyl, —C(═S)—C(═S)-aryl, —C(═S)—NH—C(═O)-aryl,—C(═S)—NH-aralkyl, —C(═S)—NH-heteroaralkyl, —C(═NH)—NH₂,—C(═NH)—(C1-C20)alkyl, —C(═NH)-aryl, —S(O)₂(C1-C20)alkyl, —S(O)₂aryl,thiomorpholinylthiocarbonyl, pyrrolidinylthiocarbonyl or —C(═S)—N(R′R″),where R′ and R″ together form a substituted or unsubstituted 5 or 6member heterocycle ring containing nitrogen and optionally having one ortwo additional hetero atoms selected from O or S; R² and R³ may be sameor different and independently represent hydrogen, halogen atom,substituted or unsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl,(C1-C20)alkoxy, aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a)represents substituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y²may be same or different and independently represent hydrogen, halogen,cyano, nitro, formyl, hydroxy, amino, substituted or unsubstitutedgroups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, (C1-C20)alkoxy, or any oneor two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″,wherein R′″ represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl,heteroaryl and aralkyl group, carboxylic acid or its derivatives; A, Band D independently represent N or —CH; their pharmaceuticallyacceptable salts and pharmaceutical compositions containing them.

BACKGROUND OF THE INVENTION

Since the discovery of penicillin, pharmaceutical companies haveproduced more than one hundred antibacterial agents to combat a widevariety of bacterial infections. In the past several years, there hasbeen rapid emergence of bacterial resistance to several of theseantibiotics. The multidrug resistance among these bacterial pathogensmay also be due to mutation leading to more virulent clinical isolation;the most disturbing milestone has been the acquisition of resistance tovancomycin, an antibiotic generally regarded as the agent of last resortfor serious Gram-positive infections. This growing multidrug resistancehas recently rekindled interest in the search for new structural classof antibiotic that inhibit or kill these bacteria possibly by novelmechanisms.

A problem of larger dimension is the increasing incidence of the morevirulent, methicillin-resistant Staphylococcus aureas (MRSA) amongclinical isolates found worldwide. As with vancomycin resistantorganisms, many MRSA strains are resistant to most of the knownantibiotics, but MRSA strains have remained sensitive to vancomycin.However, in view of the increasing reports of vancomycin resistantclinical isolates and growing problem of bacterial resistance, there isan urgent need for new molecular entities effective against the emergingand currently problematic Gram-positive organisms.

Recently, several oxazolidinones have been discovered, which inhibitprotein synthesis by binding to the 50S-ribosomal subunit which is closeto the site to which chloramphenicol and lincomycin bind but their modeof action is mechanistically distinct from these two antibiotics.

Various 1,2,3-triazoles, 1,2,4-triazoles and benzotriazoles have beenreported to show various biological activities and have therefore foundapplications in medicinal chemistry.

Some of the Literature Refences are:

(a) Chem. Pharm. Bull. 48(12), 1935-1946 (2000) discloses the triazolesof formula (ia) and (ib), which are reported as antifungal agents,

-   (b) U.S. Pat. No. 6,054,471 discloses fluorinated triazoles of the    formula (ii), which are reported for the treatment of neuropathic    pain and associated hyperalgesia, including trigeminal and herpectic    neuralgia, diabetic neuropathic pain, migraine, causalgia and    deafferentation syndromes such as brachial plexus avulsion,

(c) J. Med. Chem., 2843, 1991 discloses compound of formula (iii), whichis an anticoccidiostat and also been found to have antiproliferativeactivity in several disease models and to posses antimetastatic activityin a model of ovarian cancer progression,

(d) J. Heterocycl. Chem., 609, 1989 discloses compound of formula (iv),which is reported for anti-inflammatory effects,

(e) EPO publication no 0304221 A2 discloses compounds of formula (v),which are reported as antiproliferative reagents.

(f) PCT publication no. WO03/059894 (by Dr. Reddy's Laboratories Ltd.)discloses 1,2,3-triazoles as antibacterial agents.

The novel triazole compound of the present invention is useful for thetreatment of various infections

SUMMARY OF THE INVENTION

According to one aspect of the present invention, there is providednovel triazole compounds of the general formula (I) as defined above,their pharmaceutically acceptable salts and their pharmaceuticalcompositions containing them.

Another aspect fo the present invention provides process for thepreparation of novel triazole compounds of the formula (I).

Yet another aspect of the pesent invention provides the use of novelcompounds of formula (I) or its pharmaceutical compositions in thetreatment of bacterial infections.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to compounds having the general formula(I),

where R¹ represents halogen, azido, thioalcohol, isothiocyanate,hydroxy, isoindole-1,3-dione, substituted or unsubstituted(C1-C20)alkylsulfonyloxy, arylsulfonyloxy, (C1-C20)acyloxy group, NHR⁴where R⁴ represents hydrogen, substituted or unsubstituted groupsselected from (C1-C20)acyl, thio(C1-C20)acyl, (C1-C20)alkoxycarbonyl,(C3-C20)cycloalkoxycarbonyl, (C3-C20)cycloalkoxythiocarbonyl,(C2-C20)alkenyloxycarbonyl, (C2-C20)alkenylcarbonyl, heteroaryl,aryloxycarbonyl, heteroarylcarbonyl, heteroarylthiocarbonyl,(C1-C20)alkoxythiocarbonyl, (C2-C20)alkenyloxythiocarbonyl,aryloxythiocarbonyl, —(═O)—C(═O)—(C1-C20)alkyl, —C(═O)—C(═O)-aryl,—C(═O)—C(═O)—(C1-C20)alkoxy, —C(═O)—C(═O)-aryloxy,—C(═O)—C(═S)—(C1-C20)alkyl, —C(═O)—C(═S)-aryl, —C(═S)—S—(C1-C20)alkyl,—C(═S)—NH₂, —C(═S)—NH—(C1-C20)alkyl, —C(═S)—N—((C1-C20)alkyl)₂,—C(═S)—NH—(C2-C20)alkenyl, —C(═S)—C(═O)—(C1-C20)alkoxy,—C(═S)—C(═O)-aryloxy, —C(═S)—O—C(═O)—(C1-C20)alkyl,—C(═S)—C(═S)—(C1-C20)alkyl, —C(═S)—C(═S)-aryl, —C(═S)—NH—C(═O)-aryl,—C(═S)—NH-aralkyl, —C(═S)—NH-heteroaralkyl, —C(═NH)—NH₂,—C(═NH)—(C1-C20)alkyl, —C(═NH)-aryl, —S(O)₂(C1-C20)alkyl, —S(O)₂aryl,thiomorpholinylthiocarbonyl, pyrrolidinylthiocarbonyl or —C(═S)—N(R′R″),where R′ and R″ together form a substituted or unsubstituted 5 or 6member heterocycle ring containing nitrogen and optionally having one ortwo additional hetero atoms selected from O or S; R² and R³ may be sameor different and independently represent hydrogen, halogen atom,substituted or unsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl,(C1-C20)alkoxy, aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a)represents substituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y²may be same or different and independently represent hydrogen, halogen,cyano, nitro, formyl, hydroxy, amino, substituted or unsubstitutedgroups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, (C1-C20)alkoxy, or any oneor two of Y¹ or Y² may represent substituted or unsubstituted —CH═NOR′″,wherein R′″ represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl,heteroaryl and aralkyl group, carboxylic acid or its derivatives; A, Band D independently represent N or —CH; their pharmaceuticallyacceptable salts and pharmaceutical compositions containing them.

Suitable groups represented by R⁴ are described as (C1-C20)acyl groupsuch as —C(═O)H, —C(═O)CH₃, —C(═O)CH₂CH₃, —C(═O)(CH₂)CH₃,—C(═O)(CH₂)₃CH₃, —C(═O)(CH₂)₄CH₃, —C(═O)(CH₂)₅CH₃, —C(═O)Ph and thelike, the (C1-C20)acyl group may be substituted; thio(C1-C20)acyl groupsuch as —C(═S)H, —C(═S)CH₃, —C(═S)CH₂CH₃, —C(═S)Ph and the like, thethio(C1-C20)acyl group may be substituted; (C1-C20)alkoxycarbonyl groupcontaining (C1-C20)alkyl group which may be linear or branched such asmethoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl andthe like, the (C1-C20)alkoxycarbonyl group may be substituted;(C3-C20)cycloalkoxycarbonyl such as cyclopropoxycarbonyl,cyclobutoxycarbonyl and the like, the (C3-C20)cycloalkoxycarbonyl may besubstituted; (C3-C20)cycloalkoxythiocarbonyl such ascyclopropoxythiocarbonyl, cyclobutoxythiocarbonyl and the like, the(C3-C20)cycloalkoxythiocarbonyl may be substituted;(C2-C20)alkenylcarbonyl such as ethenylcarbonyl, propenylcarbonyl,butenylcarbonyl and the like, the (C2-C20)alkenylcarbonyl may besubstituted; heteroaryl group such as pyridyl, furyl, thiophenyl,benzothiazoyl, purinyl, benzimidazoyl, pyrimidinyl, tetrazolyl and thelike, the heteroaryl group may be substituted; heteroarylcarbonyl suchas pyridylcarbonyl, furylcarbonyl, thiophenylcarbonyl,benzothiazoylcarbonyl, benzimidazoylcarbonyl, pyrimidinylcarbonyl,pyridazinecarbonyl, pyrimidinecarbonyl, pyrazinecarbonyl,tetrazolylcarbonyl and the like, the heteroarylcarbonyl group may besubstituted, heteroarylthiocarbonyl such as pyridylthiocarbonyl,furylthiocarbonyl, thiophenylthiocarbonyl, benzothiazoylthiocarbonyl,benzimidazoylthiocarbonyl, pyrimidinylthiocarbonyl,pyridazinethiocarbonyl, pyrimidinethiocarbonyl, pyrazinethiocarbonyl,tetrazolylthiocarbonyl and the like, the heteroarylthiocarbonyl may besubstituted, (C2-C20)alkenyloxycarbonyl group such asethenyloxycarbonyl, propenyloxycarbonyl, butenyloxycarbonyl and thelike, the (C2-C20)alkenyloxycarbonyl may be substituted; aryloxycarbonylgroup such as phenoxycarbonyl, benzyloxycarbonyl group and the like, thearyloxycarbonyl group may be substituted; (C1-C20)alkoxythiocarbonylgroup such as CH₃O—C(═S)—, C₂H₅O—C(═S)—C₃H₇O—C(═S)— and the like,(C1-C20)alkoxythiocarbonyl group may be substituted;(C2-C20)alkenyloxythiocarbonyl group such as ethenyloxythiocarbonyl,propenyloxythiocarbonyl, butenyloxythiocarbonyl and the like, the(C2-C20)alkenyloxythiocarbonyl group may be substituted;aryloxythiocarbonyl group such as (phenyl)O—C(═S)—, (benzyl)O—C(═S)— andthe like, which may be substituted; —C(═O)—C(═O)—(C1-C20)alkyl groupsuch as —C(═O)—C(═O)methyl, —C(═O)—C(═O)ethyl, —C(═O)—C(═O)propyl andthe like, which may be substituted; —C(═O)—C(═O)-aryl group such as—C(═O)—C(═O)phenyl, —C(═O)—C(═O)naphthyl and the like, which may besubstituted; —C(═O)—C(═O)—(C1-C20)alkoxy group such as—C(═O)—C(═O)methoxy, —C(═O)—C(═O)ethoxy, —C(═O)—C(═O)propyloxy and thelike, which may be substituted; —C(═O)—C(═O)-aryloxy group such as—C(═O)—C(═O)phenyloxy, —C(═O)—C(═O)benzyloxy, which may be substituted;—C(═O)—C(═S)—(C1-C20)alkyl group such as —C(═O)—C(═S)-methyl,—C(═O)—C(═S)-ethyl, —C(═O)—C(═S)-propyl, —C(═O)—C(═S)-butyl and thelike, which may be substituted; —C(═O)—C(═S)-aryl group such as—C(═O)—C(═S)-phenyl, —C(═O)—C(═S)-naphthyl and the like, which may besubstituted; —(C═S)—S—(C1-C20)alkyl such as —(C═S)—S-methyl,—(C═S)—S-ethyl, —(C═S)—S-propyl and the like, which may be substituted;—(C═S)—NH₂, which may be substituted; —(C═S)—NH—(C1-C20)alkyl such as—(C═S)—NH-methyl, —(C═S)—NH-ethyl, —(C═S)—NH-propyl and the like, whichmay be substituted; —C(═S)—N—((C₁-C₆)alkyl)₂ such as —C(═S)—N-(methyl)₂,—C(═S)—N-(ethyl)₂, —C(═S)—N-(propyl)₂ and the like, which may besubstituted; —C(═S)—NH—(C2-C20)alkenyl such as —C(═S)—NH-ethenyl,—C(═S)—NH-propenyl, —C(═S)—NH-butenyl and the like, which may besubstituted; —(C═S)—(C═O)—(C1-C20)alkoxy such as —(C═S)—(C═O)-methoxy,—(C═S)—(C═O)-ethoxy, —(C═S)—(C═O)-propoxy and the like, which may besubstituted; —(C═S)—(C═O)-aryloxy such as —(C═S)—(C═O)-phenyloxy,—(C═S)—(C═O)-naphthyloxy and the like, which may be substituted;—C(═S)—O—(C═O)—(C1-C20)alkyl such as —C(═S)—O—(C═O)-methyl,—C(═S)—O—(C═O)-ethyl, —C(═S)—O—(C═O)-propyl and the like, which may besubstituted; —C(═S)—C(═S)—(C1-C20)alkyl group such as—C(═S)—C(═S)methyl, —C(═S)—C(═S)ethyl, —C(═S)—C(═S)propyl and the like,which may be substituted; —C(═S)—C(═S)aryl group such as—C(═S)—C(═S)phenyl, —C(═S)—C(═S)naphthyl and the like, which may besubstituted; —C(═S)—NH—C(═O)-aryl group such as —C(═S)—NH—C(═O)-phenyl,—C(═S)—NH—C(═O)-naphthyl and the like, —C(═S)—NH—C(═O)-aryl group may besubstituted; —C(═S)—NH-aralkyl group such as —C(═S)—NH-benzyl,—C(═S)—NH-phenethyl, —C(═S)—NH—C₆H₅CH₂CH₂CH₂, —C(═S)—NH-naphthylmethyland the like, —C(═S)—NH-aralkyl group may be substituted;—C(═S)—NH-heteroaralkyl such as —C(═S)—NH-pyridinemethyl,—C(═S)—NH-furanmethyl, —C(═S)—NH-thiophenylenemethyl,—C(═S)—NH-benzothiazolemethyl, —C(═S)—NH-benzimidazolemethyl,—C(═S)—NH-pyrimidinemethyl, —C(═S)—NH-pyrimidinemethyl,—C(═S)—NH-pyrazinemethyl, —C(═S)—NH-tetrazolemethyl and the like, where—C(═S)—NH-aralkyl group may be substituted; —C(═NH)—NH₂, which may besubstituted; —C(═NH)—(C1-C20)alkyl such as —C(═NH)-methyl,—C(═NH)-ethyl, —C(═NH)-propyl and the like, which may be substituted;—C(═NH)-aryl such as —C(═NH)-phenyl, —C(═NH)-naphthyl and the like,which may be substituted; S(O)₂—(C1-C20)alkyl such as S(O)₂-methyl,S(O)₂-ethyl, S(O)₂-propyl, S(O)₂-isopropyl, S(O)₂-butyl, S(O)₂-isobutyland the like, which may be substituted; S(O)₂-aryl such as S(O)₂-phenyl,S(O)₂-naphthyl and the like, which may be substituted;thiomorpholinylthiocarbonyl, which may be substituted;pyrrolidinylthiocarbonyl, which may be substituted; or —C(═S)—N(R′R″)where R′R″ are as defined above.

A 5 or 6 member heterocycle ring formed by R′ & R″, containing nitrogen,optionally having one or two additional heteroatoms selected fromoxygen, nitrogen or sulfur, is selected from pyrrolidinyl, pyrrolyl,morpholinyl, thiomorpholinyl, benzothiazole, benzoimidazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl and the like, the heterocycle may besubstituted.

When the groups represented by R⁴, R^(4a), R^(4b), 4^(4c), 4^(4d),R^(4e), R, R⁷ and heterocycles formed by R′ and R″ are substituted, thesubstituents may be selected from halogen atom such as chlorine,fluorine, bromine and iodine; hydroxy, amino, cyano, nitro,(C1-C20)alkyl, which is as defined as earlier; hydroxy(C1-C20)alkyl, inwhich (C1-C20)alkyl groups is as defined earlier; (C1-C20)alkoxy groupsuch as methoxy, ethoxy, propoxy and the like; ═O, ═S, aryl group suchas phenyl, naphthyl and the like, hydroxyaryl such as hydroxyphenyl,hydroxynaphthyl and the like, pyridyl, mono(C1-C20)alkylamino such asmethylamino, ethylamino, propylamino and the like; di(C1-C20)alkylaminosuch as dimethylamino, diethylamino, dipropylamino and the like;(C1-C20)acyl group such as —C(═O)H, —C(═O)CH₃, —C(═O)CH₂CH₃,—C(═O)(CH₂)₂CH₃, —C(═O)(CH₂)₃CH₃, —C(═O)(CH₂)₄CH₃, —C(═O)(CH₂)₅CH₃,—C(═O)Ph and the like; thio(C1-C20)acyl group such as —C(═S)H,—C(═S)CH₃, —C(═S)CH₂CH₃, —C(═S)Ph and the like; (C1-C20)alkoxycarbonylgroup such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,butoxycarbony, tert-butoxycarbonyl(BOC) and the like; (C1-C20)alkoxyarylgroup such as methoxyaryl, ethoxyaryl, propoxyaryl, iso-propoxyaryl,butoxyaryl and the like, where aryl group is as defined above orcarboxylic acid or its derivatives selected from amides and esters suchas CONH₂, CONHMe, CONMe₂, CONHEt, CONEt₂, CONHPh, COOCH₃, COOC₂H₅ orCOOC₃H₇.

Suitable groups represented by R² and R³ may be selected from hydrogen,halogen atom such as fluorine, chlorine or bromine; substituted orunsubstituted (C1-C20)alkyl group such as methyl, ethyl, n-propyl,isopropyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl, n-hexyland the like; halo(C1-C20)alkyl group such as halomethyl, haloethyl,halopropyl, trihalomethyl and the like, wherein the halo group isselected from fluorine, chlorine, bromine or iodine; (C1-C20)alkoxygroup such as methyl, ethyl, propyl and the like; aryl group such asphenyl, naphthyl and the like; heteroaryl groups such as pyridyl,thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl andthe like; cyano, nitro; OR^(a) where R^(a) represents substituted orunsubstituted (C1-C20)alkyl group such as methyl, ethyl, propyl,isopropyl and the like.

Suitable substitutents on R² and R³ are selected from hydroxy, halogen,nitro, amino, (C1-C20)alkyl, (C1-C20)alkoxy, ═O, ═S, cyano group, orcarboxylic acid or its derivatives. These groups are as defined above.

Suitable substitutents on R^(a) are selected from hydroxy, halogen,nitro, amino, (C1-C20)alkyl, (C1-C20)alkoxy, cyano group, or carboxylicacid or its derivatives. These groups are as defined above.

Suitable groups represented by Y¹ and Y² are selected from hydrogen,cyano, nitro, formyl, hydroxy, amino, halogen such as fluorine,chlorine, bromine or iodine; substituted or unsubstituted (C1-C20)alkylsuch as methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, t-butyland the like, which may be substituted; hydroxy(C1-C20)alkyl such ashydroxymethyl, hydroxyethyl, hydroxypropyl and the like, which may besubstituted; dihydroxy(C1-C20)alkyl such as dihydroxymethyl,dihydroxyethyl, dihydroxypropyl and the like, which may be substituted;(C1-C20)alkoxy(C1-C20)alkyl group such as methoxymethyl, methoxyethyl,ethoxyethyl, ethoxymethyl, methoxypropyl, propoxymethyl, propoxyethyland the like, which may be substituted; (C1-C20)alkylcarbonyl group suchas methylcarbonyl, ethylcarbonyl and the like, which may be substituted;(C1-C20)alkoxycarbonyl group such as methoxycarbonyl, ethoxycarbonyl andthe like, which may be substituted; carboxy(C1-C20)alkyl such as—CH₂—COOH, —CH₂—CH₂—COOH and the like, which may be substituted;(C1-C20)alkylsulfonyl group such as methylsulfonyl, ethylsulfonyl andthe like, which may be substituted;(C1-C20)alkylcarbonylamino(C1-C20)alkyl groups such asmethylcarbonylaminomethyl, ethylcarbonylaminomethyl,methylcarbonylaminoethyl and the like, which may be substituted;arylcarbonylamino(C1-C20)alkyl such as phenylcarbonylaminomethyl,phenylcarbonylaminoethyl and the like, which may be substituted;(C1-C20)alkyl aminocarbonyl group such as methylaminocarbonyl,ethylaminocarbonyl, propylaminocarbonyl and the like, which may besubstituted; (C1-C20)alkylcarbonyloxy(C1-C20)alkyl group such asmethylcarbonyloxymethyl, ethylcarbonylxoymethyl, methylcarbonyloxyethyl,propylcarbonyloxymethyl, propylcarbonyloxyethyl, propylcarbonyloxypropyland the like, which may be substituted; amino(C1-C20)alkyl such asaminomethyl, aminoethyl, aminopropyl and the like, which may besubstituted; mono(C1-C20)alkylamino such as methylamino, ethylamino,propylamino and the like, which may be substituted; di(C1-C20)alkylaminosuch as dimethylamino, diethylamino, dipropylamino and the like, whichmay be substituted; (C1-C20)alkoxy group such as methoxy, ethoxy,propoxy, isopropoxy and the like, which may be substituted; Any of Y¹ orY² may also represent substituted or unsubstituted —CH═NOR′″, whereinR′″ represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryland aralkyl group, carboxylic acid or its derivatives may be amides oresters. Exemplary carboxylic acid groups include CONH₂, CONHMe, CONMe₂,CONHEt, CONEt₂, CONHPh, COOCH₃, COOC₂H₅ or COOC₃H₇.

When the groups represented by Y¹ and Y² are substituted, thesubstituents may be selected from hydroxy, nitro, cyano, amino,tert-butyldimethylsilyloxy (TBSO), halogen atom, (C1-C20)alkyl,(C1-C20)alkoxy, (C3-C20)cycloalkyl, aryl, benzyloxy, acyl or acyloxygroup such as formyloxy, acetyloxy and the like, carboxylic acid or itsesters. The groups are as defined above.

When the groups represented by R^(c) and R^(d) as defined below aresubstituted, the substituents are selected from halogen, hydroxy, nitro,amino, cyano, (C1-C20)alkyl or (C1-C20)alkoxy. (C1-C20)alkyl and(C1-C20)alkoxy are as defined above.

The groups (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl and aralkylgroup defined for R′″ are as defined earlier.

When the suitable cites of the above defined groups are substituted,mono, di or tri substitutions are possible.

One aspect of the present invention provides compounds of the formula(I),

R¹ represents NHR⁴ where R⁴ represents (C1-C20)acyl,C1-C20)alkoxycarbonyl;

R² and R³ may be same or different and independently represent hydrogen,halogen atom, (C1-C20)alkyl group, halo(C1-C20)alkyl;

Y¹ and Y² may be same or different and independently represent hydrogen,halogen, cyano, nitro, formyl, hydroxy, amino, substituted orunsubstituted groups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, (C1-C20)alkoxy, or any oneor two of Y¹ or Y² may represent substituted or unsubstituted —CH═NOR′″,wherein R′″ represents hydrogen and (C1-C20)alkyl group, carboxylic acidor its derivatives; their pharmaceutically acceptable salts.

Another aspect of the compound of the formula (I), R¹ represents NHR⁴where R⁴ represents (C1-C20)acyl, C1-C20)alkoxycarbonyl;

R² and R³ may be same or different and independently represent hydrogen,halogen atom, halo(C1-C20)alkyl;

Y¹ and Y² may be same or different and independently represent hydrogen,cyano, halogen, nitro, formyl, hydroxy, amino, substituted orunsubstituted groups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, amino(C1-C20)alkyl, mono(C1-C20)alkylamino,di(C1-C20)alkylamino, (C1-C20)alkoxy, or any one or two of Y¹ or Y² mayrepresent substituted or unsubstituted —CH═NOH, carboxylic acid or itsderivatives. The substituents on Y¹ and Y² may be selected from hydroxy,cyano, amino, (C1-C20)alkyl, (C1-C20)alkoxy, acyl, carboxylic acid orits esters; their pharmaceutically acceptable salts.

Another aspect of the present invention provides compound of the formula(I),₁₃ R¹ represents NHR⁴ where R⁴ represents thio(C1-C20)acyl,(C1-C20)alkoxythiocarbonyl,

R² and R³ may be same or different and independently represent hydrogen,halogen atom, (C1-C20)alkyl group, halo(C1-C20)alkyl;

Y¹ and Y² may be same or different and independently represent hydrogen,halogen, cyano, nitro, formyl, hydroxy, amino, substituted orunsubstituted groups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkyl amino, di(C1-C20)alkylamino, (C1-C20)alkoxy, or anyone or two of Y¹ or Y² may represent substituted or unsubstituted—CH—NOR′″, wherein R′″ represents hydrogen and (C1-C20)alkyl group,carboxylic acid or its derivatives; their pharmaceutically acceptablesalts.

In another aspect of the compound of the formula (I),_R¹ represents NHR⁴where R⁴ represents thio(C1-C20)acyl, (C1-C20)alkoxythiocarbonyl,

R² and R³ may be same or different and independently represent hydrogen,halogen atom, halo(C1-C20)alkyl;

Y¹ and Y² may be same or different and independently represent hydrogen,cyano, halogen, nitro, formyl, hydroxy, amino, substituted orunsubstituted groups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, amino(C1-C20)alkyl, mono(C1-C20)alkylamino,di(C1-C20)alkylamino, (C1-C20)alkoxy, or any one or two of Y¹ or Y² mayrepresent substituted or unsubstituted —CH═NOH, carboxylic acid or itsderivatives. The substituents on Y¹ and Y² may be selected from hydroxy,cyano, amino, (C1-C20)alkyl, (C1-C20)alkoxy, acyl, carboxylic acid orits esters; their pharmaceutically acceptable salts.

Pharmaceutically acceptable salts forming part of this invention includesalts derived from inorganic bases such as Li, Na, K, Ca, Mg, Fe, Cu,Zn, Mn; salts of organic bases such as N,N′-diacetylethylenediamine,betaine, caffeine, 2-diethylaminoethanol, 2-dimethylaminoethanol,N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine,hydrabamine, isopropylamine, methylglucamine, morpholine, piperazine,piperidine, procaine, purines, theobromine, triethylamine,trimethylamine, tripropylamine, tromethamine, diethanolamine, meglumine,ethylenediamine, N,N′-diphenylethylenediamine,N,N′-dibenzylethylenediamine, N-benzyl phenylethylamine, choline,choline hydroxide, dicyclohexylamine, metformin, benzylamine,phenylethylamine, dialkylamine, trialkylamine, thiamine,aminopyrimidine, aminopyridine, purine, spermidine, and the like; chiralbases like alkylphenylamine, glycinol, phenyl glycinol and the like,salts of natural amino acids such as glycine, alanine, valine, leucine,isoleucine, norleucine, tyrosine, cystine, cysteine, methionine,proline, hydroxy proline, histidine, ornithine, lysine, arginine,serine, threonine, phenylalanine; unnatural amino acids such asD-isomers or substituted amino acids; guanidine, substituted guanidinewherein the substituents are selected from nitro, amino, alkyl such asmethyl, ethyl, propyl and the like; alkenyl such as ethenyl, propenyl,butenyl and the like; alkynyl such as ethynyl, propynyl and the like;ammnonium or substituted ammonium salts and aluminum salts. Salts mayinclude acid addition salts where appropriate which are, sulphates,nitrates, phosphates, perchlorates, borates, halides, acetates,tartrates, maleates, citrates, succinates, palmoates,methanesulphonates, benzoates, salicylates, hydroxynaphthoates,benzenesulfonates, ascorbates, glycerophosphates, ketoglutarates and thelike.

Particularly preferred compounds according to this invention are

Another group of particulary useful compounds of the present inventionare

Another group of particulary useful compounds of the present inventionare

Another group of particulary useful compounds of the present inventionare

Yet another group of compounds of the present invention are

A preferred compound of the present invention is

A preferred compound of the present invention is

A preferred compound of the present invention is

A preferred compound of the present invention is

A preferred compound of the present invention is

A preferred compound of the present invention is

Yet another aspect of the present invention provides preparation of thethe novel compounds of the present invention according to the procedureof the following schemes, using appropriate materials Those skilled inthe art will readily understand that known variations of the conditionsand processes of the following preparative procedures can be used toprepare these compounds. All temperatures are degrees Celsius unlessotherwise noted.

The following Schemes describe procedures for making representativecompounds of the present invention. Moreover, by utilizing theprocedures described in detail, one of ordinary skill in the art canreadily prepare additional compounds of the present invention claimedherein.

The process for the preparation of compounds of formula (I), where R¹represents azido and all other symbols are as defined earlier, whichcomprises:

(i) reacting the compound of formula (Ia)

where X represents halogen atom such as fluorine, chlorine, bromine andthe like; R² and R³ are as defined earlier, with a compound of formula(Ib)

where A, B, D, Y¹ and Y² are as defined earlier, to produce a compoundof formula (Ic)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier,

(ii) reducing the compund of formula (Ic) by using reducing agent to acompound of formula (Id)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier,

(iii) converting the compound of formula (Id) to a compound of formula(Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier,

(iv) converting the compound of formula (Ie) to a compound of formula(If)

where R^(c) represents substituted or unsubstituted (C1-C20)alkyl groupsuch as methyl, ethyl, n-propyl, iso-propyl and the like; A, B, D, Y¹,Y², R² and R³ are as defined earlier,

(v) reducing the compound of formula (If), to give a compound of formula(I)

where R¹ represents hydroxy group; A, B, D, Y¹, Y², R² and R³ are asdefined earlier,

(vi) converting the compound of formula (I), where R¹ represents hydroxygroup, to a compound of formula (I), where R¹ represents substituted orunsubstituted (C1-C20)alkyl sulfonyloxy or arylsulfonyloxy group and allother symbols are as defined earlier, and

(vii) converting the compound of formula (I) where R¹ representssubstituted or unsubstituted (C1-C20)alkylsulfonyloxy or arylsulfonyloxygroup, to a compound of formula (I) where R¹ represents azido group andall other symbols are as defined earlier.

The compound of formula (Ic) may be prepared by reacting a compound offormula (Ia) with a compound of formula (Ib) by using a base such aspotassium hydroxide (KOH), sodium hydroxide (NaOH), potassium carbonate(K₂CO₃), sodium carbonate (Na₂CO₃), sodium hydride (NaH), potassiumhydride (KH), triethylamine, diisopropylethyl amine and the like. Thereaction may be carried out using a solvent such as diemthyl sulfoxide(DMSO), dimethylformamide (DMF), tetrahydrofuran (THF), acetonitrile,chloroform, nitrobenzene and the like or mixtures thereof. The reactionmay be carried out in inert atmosphere, which may be maintained usinginert gases such as N₂ or Ar. The reaction may be carried out at atemperature in the range of 20 to 100° C., preferably at a temperaturein the range of ambient—80° C. The reaction time may range from 1 to 15h, preferably from 6 to 12 h.

The reduction of a compound of formula (Ic) to produce a compound offormula (Id) may be carried out in the presence of reducing agents suchas NiCl₂/NaBH₄, lithium aluminium hydride (LAH), gaseous hydrogen and acatalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such as charcoal,alumina, asbestos and the like. The reduction may be carried out in thepresence of a solvent such as dioxane, acetic acid, ethyl acetate, THF,alcohol such as methanol, ethanol and the like or mixtures thereof. Apressure between atmospheric pressure to 60 psi may be used. Thereaction may be carried out at a temperature from 0 to 60° C.,preferably at 0 to room temperature. The reaction time ranges from 0.5to 48 h, preferably in the range of 0.5 to 5 h. The reduction may alsobe carried out by employing metal in mineral acids such as Sn/HCl,Fe/HCl, Zn/HCl, Zn/CH₃CO₂H and the like.

The compound of formula (Id) may be converted to a compound of formula(Ie) by using sodium nitrite (NaNO₂) in the presence of HCl or aceticacid (CH₃COOH) followed by sodiumazide (NaN₃). The temperature of thereaction may be maintained in the range of −40° C. to boilingtemperature, preferably in the range of 0° C. to room temperature. Theduration of the reaction may be in the range of 0.5 to 15 h, preferablyin the range of 0.5 to 5 h.

The compound of formula (If) may be prepared by heating a compound offormula (Ie) with (C₁-C₆)alkyl ester of propiolic acid. The solvent usedin the reaction may be selected from benzene, toluene, xylene,acetonitrile, THF, DMF and the like. The temperature of the reaction maybe maintained in the range of 10 to 200° C., preferably in the range ofroom temperature to the boiling temperature of the solvent. The durationof the reaction may be in the range of 1 to 25 h, preferably 5 to 20 h.

The conversion of compound of formula (If) to a compound of formula (I),where R¹ represents hydroxy may be carried out by using reducing agentssuch as LAH, lithiumboronhydride (LiBH₄) or sodiumtetrahydroborate/iodine (NaBH₄/I₂). The reaction may be carried out inthe presence of a solvent such as methanol, ethanol, THF, diethylether(Et₂O), dioxane and the like, or mixtures thereof. The temperature ofthe reaction may be in the range of −80 to 100° C., preferably 0° C. toboiling temperature of the solvent. The duration of the reaction may bein the range of 0.5 to 10 h.

The compound of formula (I) where R¹ represents OH may be converted tocompound of formula (I) where R¹ represents substituted or unsubstituted(C1-C20)alkylsulfonyloxy or arylsulfonyloxy group, by treating withalkylsulfonylchloride or arylsulfonylchloride such as methanesulfonylchloride, p-toluenesulfonyl chloride and the like. The reaction may becarried out in the presence of chloroform, dichloromethane, THF, dioxaneand the like or mixtures thereof. The base used in the reaction may beselected from Et₃N, diisopropyl ethylamine, Na₂CO₃, K₂CO₃ and the like.The temperature of the reaction may be maintained in the range of 0 to50° C., preferably in the range of 0 to room temperature. The durationof the reaction may be in the range of 1 to 12 h, preferably in therange of 1 to 4 h.

The compound of formula (I) where R¹ represents substituted orunsubstituted (C1-C20)alkyl sulfonyloxy or arylsulfonyloxy group may beconverted to compound of formula (I) wherein R¹ represents azido group,by treating with NaN₃. The solvent used in the reaction may be selectedfrom DMF, DMSO, acetonitrile, nitromethane and the like. Thetempearature of the reaction may be maintained in the range of roomtemperature to 120° C., preferably room temperature to 80° C. Theduration of the reaction may be in the range of 1 to 12 h, preferably 1to 4 h.

Alternatively, the compound of formula (I) wherein R¹ represents hydroxycan be converted to a compound of formula (I) wherein R¹ representsazido group without isolating and characterizing the alkyl sulfonyl orarylsulfonyl intermediate formed.

Another embodiment of the present invention provides an alternativeprocess for the preparation of the compound of formula (I) where R¹represents azido and all other symbols are as defined earlier, whichcomprises:

(i) converting the compound of formula (Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier, to a compoundof formula (I)

where R¹ represents hydroxy; A, B, D, Y¹, Y², R² and R³ are as definedearlier and

(ii) reacting the compound of formula (I) where R¹ represents hydroxygroup, with MsCl, triethylamine and sodium azide to give a compound offormula (I) where R¹ represents azido group and all other symbols are asdefined above

The compound of formula (Ie) may be converted to a compound of formula(I), where R¹ represents hydroxy group, by treating with propargylalcohol. The solvent used in the reaction may be selected from benzene,toluene, xylene, acetonitrile, THF and the like. The temperature of thereaction may be maintained in the range of 10 to 200° C., preferablyroom temperature to the boiling temperature of the solvent. The durationof the reaction may be in the range of 1 to 25 h, preferably in therange of 5 to 20 h.

The compound of formula (I) where R¹ represents hydroxy group may beconverted to a compound of formula (I) where R¹ represents azido groupwas carried out in two steps. In step (1) the compound of formula (I)where R¹ represents OH is converted to compound of formula (I) where R¹represents leaving group such as halogen atom, by treating withCBr₄/PPh₃, PBr₃, thionylchloride (SOCl₂) and the like. The reaction maybe carried out in the presence of chloroform, dichloromethane, THF,dioxane and the like or mixtures thereof. The temperature of thereaction may be maintained in the range of 0 to 80° C., preferably inthe range of 0 to 50° C. The duration of the reaction may be in therange of 1-12 h, preferably in the range of 1-4 h. In step (2), thecompound of formula (I) where R¹ represents halogen atom may beconverted to compound of formula (I) where R¹ represents azido group bytreating with NaN₃, LiN₃, trialkylsilylazide and the like. The solventused in the reaction may be selected from acetone, THF, DMF, dimethylsulfoxide (DMSO), acetonitrile and the like. The temperature of thereaction may be maintained in the range of room temperature to 120° C.,preferably room temperature to 80° C. The duration of the reaction maybe in the range of 1 to 12 h, preferably 1 to 4 h.

Yet another embodiment of the present invention provides an alternativeprocess for the preparation of compound of formula (I), where R¹represents azido group, which comprises:

(i) converting the compound of formula (Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier, to a compoundof formula (I)

where R¹ represents halogen atom such as chlorine, bromine and the like,and all other symbols are as defined earlier and

(ii) converting the compound of formula (I) where R¹ represents halogenatom such as chlorine, bromine and the like, to a compound of formula(I), wherein R¹ represents azido group.

The compound of formula (I), where R¹ represents halogen atom such aschlorine, bromine and the like, may be prepared from a compound offormula (Ie) by using propargyl halide such as propargylchloride orpropargyl bromide. The solvent used in the reaction may be selected frombenzene, toluene, xylene, acetonitrile, THF and the like. Thetemperature of the reaction may be maintained in the range of 10 to 200°C., preferably room temperature to the boiling temperature of thesolvent. The duration of the reaction may be in the range of 1 to 25 h,preferably in the range of 5 to 20 h.

The conversion of a compound of formula (I) where R¹ represents halogenatom such as chlorine, bromine and the like, to a compound of formula(I) where R¹ represents azido group, may be carried out in the presenceof one or more equivalents of metal azide such as LiN₃, NaN₃ or trialkylsilylazide. The reaction may be carried out in the presence of solventsuch as THF, acetone, DMF, DMSO and the like or mixtures thereof. Thereaction may be carried out in inert atmosphere, which may be maintainedusing N₂ or Ar. The reaction may be carried out at a temperature in therange of ambient temperature to reflux temperature of the solvent,preferably at a temperature in the range of 50 to 80° C. The reactiontime may be in the range from 0.5 to 18 h, preferably 1 to 4 h.

Another embodiment of the present invention provides a process for thepreparation of compound of formula (I) where R¹ represents NHR⁴ whereinR⁴ represents hydrogen atom, which comprises:

(i) converting the compound of formula (If)

where R^(c) represents substituted or unsubstituted (C1-C20)alkyl groupsuch as methyl, ethyl, n-propyl, iso-propyl and the like; A, B, D, Y¹,Y², R² and R³ are as defined earlier, to a compound of formula (Ig)

where all symbols are as defined earlier and

(ii) reducing the compound of formula (Ig), to produce a compound offormula (I)

where R¹ represents NHR⁴ wherein R⁴ represents hydrogen atom and allother symbols are as defined earlier.

The conversion of compound of formula (If) to a compound of formula (Ig)may be carried out in the presence of ammonia solution in water oralcohol. The temperature of the reaction may be in the range of −40 to50° C., preferably of 0° C. to room temperature. The duration of thereaction may be in the range of 0.5 to 12 h, preferably 0.5 to 4 h.

The reduction of compound of formula (Ig) to a compound of formula (I),where R¹ represents NHR⁴ wherein R⁴ represents hydrogen atom, may becarried out by using borane complex in THF, diethylether, SMe₂ or amine.The solvent used in the reaction may be selected from THF, diethylether,dioxane and the like. The temperature of the reaction may be in therange of −20 to 70° C., preferably 0 to boiling temperature of thesolvent. The duration of the reaction may be in the range of 1 to 15 h,preferably 1 to 6 h.

Yet another embodiment of the present invention provides an alternativeprocess for the preparation of compound of formula (I) where R¹represents NHR⁴ wherein R⁴ represents hydrogen atom, which comprises:

(i) reducing the compound of formula (I) wherein R¹ represents azidogroup, to produce compound of formula (I)

where R¹ represents NHR⁴ wherein R⁴ represents hydrogen atom; A, B, D,Y¹, Y², R² and R³ are as defined earlier.

The reduction of a compound of formula (I) where R¹ represents azidogroup, to produce a compound of formula (I) where R¹ represents NHR⁴wherein R⁴ represents hydrogen atom, may be carried out in the presenceof gaseous hydrogen and a catalyst such as Ru, Pd, Rh, Pt, Ni on solidbeads such as charcoal, alumina, asbestos and the like. The reductionmay be carried out in the presence of a solvent such as dioxane, aceticacid, ethyl acetate, THF, alcohol such as methanol, ethanol and the likeor mixtures thereof. A pressure between atmospheric pressure to 60 psimay be used. The reaction may be carried out at a temperature in therange of 25 to 60° C., preferably at room temperature. The duration ofthe reaction may be in the range of 2 to 48 h. The reduction may also becarried out by employing PPh₃ in water.

Another embodiment of the present invention provides a process for thepreparation of compound of formula (I) where R¹ represents hydroxygroup, which comprises:

(i) converting the compound of formula (Ie),

where A, B, D, Y¹, Y², R² and R³ are as defined earlier, to a compoundof formula (I),

where R¹ represents substituted or unsubstituted (C1-C20)acyloxy group,and all other symbols are as defined earlier and

(ii) hydrolysis of the compound of formula (I) where R¹ represents(C1-C20)acyloxy group, to a compound of formula (I), where R¹ representshydroxy group and all other symbols are as defined earlier.

The conversion of compound of formula (Ie) to a compound of formula (I)where R¹ represents (C1-C20)acyloxy group, may be carried out in thepresence of esters ((C1-C20)alkyl or aryl)of propargyl alcohol. Thesolvent used in the reaction may be selected from benzene, toluene,xylene, acetonitrile, THF and the like. The temperature of the reactionmay be maintained in the range of 10 to 200° C., preferably roomtemperature to the boiling temperature of the solvent. The duration ofthe reaction may be in the range of 1 to 25 h, preferably in the rangeof 5 to 20 h.

The hydrolysis of compound of formula (I) where R¹ represents(C1-C20)acyloxy, group, to a compound of formula (I), where R¹represents hydroxy group, may be carried out by using conventional esterhydrolysis procedures.

The present invention also relates to a process for the preparation ofthe compound of formula (I) where R¹ represents azido and all othersymbols are as defined earlier, which comprises:

(i) reacting the compound of formula (Ia)

where X represents halogen atom such as fluorine, chlorine, bromine andthe like; R² and R³ are as defined earlier, with a compound of formula(II)

where M represents metal atom such as sodium, potassium and the like, toproduce a compound of formula (2m)

where R² and R³ are as defined earlier,

(ii) reducing the compound of formula (Im) by using reducing agent to acompound of formula (In)

where R² and R³ are as defined earlier,

(iii) converting the compound of formula (In) to a compound of formula(Io)

where R² and R³ are as defined earlier,

(iv) reacting the compound of formula (Io), with compound of formula(Ip)

where R¹ is as defined in the description, to obtain a compound offormula (Iq)

where R¹ represents NHR⁴ wherein R⁴ is as defined in the description, R²and R³ are as defined earlier,

(v) converting the compound of formula (Iq), to a compound of formula(Ir)

where R¹ is as defined above, R² and R³ are as defined earlier,

(vi) converting the compound of formula (Ir), to a compound of formula(I)

where R¹ is as defined above; R² and R³ are as defined earlier,

The compound of formula (Im) may be prepared by reacting a compound offormula (Ia) with a compound of formula (II). The reaction may becarried out using a solvent such as DMSO, DMF, THF, acetonitrile,chloroform, nitrobenzene and the like or mixtures thereof. The reactionmay be carried out in inert atmosphere, which may be maintained usinginert gases such as N₂ or argon (Ar). The reaction may be carried out ata temperature in the range of 20 to 100° C., preferably at a temperaturein the range of ambient to 80° C. The reaction time may range from 1 to15 h, preferably from 6 to 12 h.

The reduction of a compound of formula (Im) to produce a compound offormula (In) may be carried out in the presence of reducing agents suchas NiCl₂/NaBH₄, lithium aluminium hydride (LAH), gaseous hydrogen and acatalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such as charcoal,alumina, asbestos and the like. The reduction may be carried out in thepresence of a solvent such as dioxane, acetic acid, ethyl acetate, THF,alcohol such as methanol, ethanol and the like or mixtures thereof. Apressure between atmospheric pressure to 60 psi may be used. Thereaction may be carried out at a temperature from 0 to 60° C.,preferably at 0 to room temperature. The reaction time ranges from 0.5to 48 h, preferably in the range of 0.5 to 5 h. The reduction may alsobe carried out by employing metal in mineral acids such Sn/HCl, Fe/HCl,Zn/HCl, Zn/CH₃CO₂H and the like.

The compound of formula (In) may be converted to a compound of formula(Io) by using NaNO₂ in the presence of HCl or CH₃COOH followed by NaN₃.The temperature of the reaction may be maintained in the range of −40°C. to boiling temperature, preferably in the range of 0° C. to roomtemperature. The duration of the reaction may be in the range of 0.5 to15 h, preferably in the range of 0.5 to 5 h.

Alternatively, the compound of formula (In) is converted to a compoundof formula (Io) by using alkylnitrite such as t-butylnitrite and thelike along with alkali metal azide such as sodium azide, potassium azideand the like. The solvent used in the reaction is selected from benzene,toluene, DMF, alcohol such as methanol, ethanol, propanol, isopropanol,butanol, tertiary butanol and the like. The temperature of the reactionmay be maintained in the range of −40° C. to boiling temperature,preferably in the range of 0° C. to room temperature. The duration ofthe reaction may be in the range of 0.5 to 15 h, preferably in the rangeof 0.5 to 5 h.

The compound of formula (Io) is reacted with compound of formula (Ip),to obtain a compound of formula (Iq) by using Cu(I) halide in thepresence or absence of a base such as DMAP, pyridine, triethylamine,diisopropylethylamine, lutidine and the like. The solvent used in thereaction may be selected from DMF, DMSO, THF, ether, dioxane,acetonitrile and the like.

The compound of formula (Iq) is converted to a compound of formula (Ir)by using hydrazine hydrate or an amine such as methylamine, ethylamine,ethylene diamine etc. The solvent used in the reaction is selected frommethanol, ethanol, propanol, isopropanol and the like or mixturesthereof.

The compound of formula (Ir) is converted to a compound of formula (I),by treating with 2,5-dimethoxytetrahydrofuran or2,5-dimethoxytetrahydrofuran-3-carboxaldehyde. The solvent used in thereaction is selected from acetic acid, propanoic acid and the like. Thetemperature of the reaction is maintained in the range of −20° C. toboiling temperature of the solvent used. The duration of the reaction isin the range of 0.5 to 15 h, preferably 0.5 to 10 h.

Another embodiment of the present invention provides a process for thepreparation of compound of formula (I), where R¹ represents azido group,which comprises:

(i) converting the compound of formula (Io)

where R² and R³ are as defined earlier, to a compound of formula (Is)

where R² and R³ are as defined earlier.

(ii) converting the compound of formula (Is), to a compound of formula(Ie)

where all symbols are as defined earlier and

(iii) reacting the compound of formula (Ie), with a compound of formula(Ip)

where R¹ is as defined in the description, to a compound of formula (I)

where R¹ is as defined in the description and all other symbols are asdefined earlier

The compound of formula (Io) is converted to a compound of formula (Is)by using hydrazine hydrate or an amine such as methylamine, ethylamine,ethylene diamine etc. The solvent used in the reaction is selected frommethanol, ethanol, propanol, isopropanol and the like or mixturesthereof.

The compound of formula (Is) is converted to a compound of formula (Ie),by treating with 2,5-dihydroxymethoxytetrahydrofuran or2,5-dimethoxytetrahydro-3-carboxaldehyde. The solvent used in thereaction is selected from acetic acid, propanoic acid and the like. Thetemperature of the reaction is maintained in the range of −20° C. toboiling temperature of the solvent used. The duration of the reaction isin the range of 0.5 to 15 h, preferably 0.5 to 10 h.

The compound of formula (Ie) is reacted with compound of formula (Ip),to obtain a compound of formula (I) by using Cu(I) halide. The solventused in the reaction may be selected from DMF, DMSO, THF, ether,dioxane, acetonitrile and the like.

Another embodiment of the present invention provides an alternateprocess for the preparation of compound of formula (Ir), whichcomprises:

(i) converting the compound of formula (Iu)

where R² and R³ are as defined earlier, to a compound of formula (Iv)

where R² and R³ are as defined earlier,

(ii) reacting the compound of formula (Iv), with a compound of formula(Ip)

where R¹ is as defined in the description, to a compound of formula (Ir)

where R¹ is as defined in the description, R² and R³ are as definedearlier,

(iii) reducing the compound of formula (Iw), to a compound of formula(Ir)

where all symbols are as defined above.

The compound of formula (Iu) may be converted to a compound of formula(Iv) by using NaNO₂ in the presence of HCl or CH₃COOH followed by NaN₃.The temperature of the reaction may be maintained in the range of −40°C. to boiling temperature, preferably in the range of 0° C. to roomtemperature. The duration of the reaction may be in the range of 0.5 to15 h, preferably in the range of 0.5 to 5 h.

Alternatively, the compound of formula (Iu) is converted to a compoundof formula (Iv) by using alkyl nitrite such as t-butylnitrite and thelike along with alkali metal azide such as sodium azide, potassium azideand the like. The solvent used in the reaction is selected from benzene,toluene, DMF, alcohol such as methanol, ethanol, propanol, isopropanol,butanol, tertiary butanol and the like. The temperature of the reactionmay be maintained in the range of −40° C. to boiling temperature,preferably in the range of 0° C. to room temperature. The duration ofthe reaction may be in the range of 0.5 to 15 h, preferably in the rangeof 0.5 to 5 h.

The compound of formula (Iv) is reacted with compound of formula (Ip),to obtain a compound of formula (Iw) by using Cu(I) halide in thepresence or absence of a base such as 4-(dimethylamino)pyridine (DMAP),pyridine, triethylamine, diisopropylethylamine, lutidine and the like.The solvent used in the reaction may be selected from DMF, DMSO, THF,ether, dioxane, acetonitrile and the like.

The reduction of a compound of formula (Iw) to produce a compound offormula (Ir) may be carried out in the presence of reducing agent suchas NiCl₂/NaBH₄, lithium aluminium hydride (LAH), gaseous hydrogen and acatalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such as charcoal,alumina, asbestos and the like. The reduction may be carried out in thepresence of a solvent such as dioxane, acetic acid, ethyl acetate, THF,alcohol such as methanol, ethanol and the like or mixtures thereof. Apressure between atmospheric pressure to 60 psi may be used. Thereaction may be carried out at a temperature from 0 to 60° C.,preferably at 0 to room temperature. The reaction time ranges from 0.5to 48 h, preferably in the range of 0.5 to 5 h. The reduction may alsobe carried out by employing metal in mineral acids such Sn/HCl, Fe/HCl,Zn/HCl, Zn/CH₃CO₂H, Fe/NH₄Cl and the like.

Yet another embodiment of the present invention provides a process forthe preparation of compound of formula (I), where R¹ represents NHR⁴,wherein R⁴ represents substituted or unsubstituted acetyl group and allother symbols are as defined earlier, from a compound of formula (I)where R¹ represents azido group,

where A, B, D, Y¹, Y², R² and R³ are as defined earlier.

The compound of formula (I), where R¹ represents NHR⁴, wherein R⁴represents substituted or unsubstituted acetyl group may be preparedfrom compound of formula (I), where R¹ represents azido group may becarried out by using thiolacetic acid with or without using solvent suchas THF, DMF, toluene and the like. The reaction may be carried out at atemperature in the range of 25 to 40° C., preferably at roomtemperature. The duration of the reaction may be in the range from 3 to24 h, preferably from 4 to 12 h.

Still another embodiment of the present invention provides a process forthe preparation of compound of formula (I), where R¹ represents NHR⁴,where R⁴ represents substituted or unsubstituted —C(═S)—R^(4a), whereinR^(4a) represents (C1-C20)alkyl, halo(C1-C20)alkyl, aryl, heteroaryl,—C(═O)—(C1-C20)alkoxy, —C(═O)—(C1-C20)alkoxy, —C(═O)-aryloxy,—C(═S)—(C1-C20)alkyl or —C(═S)-aryl; from compound of formula (I), whereR¹ represents NHR⁴, where R⁴ represents substituted or unsubstituted—C(═O)—R^(4a), wherein R^(4a) represents (C1-C20)alkyl,halo(C1-C20)alkyl, aryl, heteroaryl, —C(═O)—(C1-C20)alkoxy,—C(═O)-aryloxy, —C(═S)—(C1-C20)alkyl or —C(═S)-aryl

where all symbols are as defined earlier.

The compound of formula (I), where R¹ represents NHR⁴, wherein R⁴represents substituted or unsubstituted —C(═S)—R^(4a), from compound offormula (I), where R¹ represents NHR⁴, wherein R⁴ represents substitutedor unsubstituted —C(═O)—R^(4a), wherein R^(4a) is as defined above, maybe carried out by taking a solution of the amide and Lawesson's reagent(2,4-bis(methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide) indry dioxane, toluene, THF, DMF and the like. The reaction may be carriedout at a temperature in the range of room temperature to 130° C.,preferably in the range of 55 to 90° C. The duration of the reaction maybe in the range from 3 to 24 h, preferably from 3 to 10 h.

Another embodiment of the present invention provides a process for thepreparation of compound of formula (I), where R¹ represents NHR⁴,wherein R⁴ represents substituted or unsubstituted —C(═S)—OR^(4b),wherein R^(4b) represents (C1-C20)alkyl, (C3-C20)cycloalkyl, aryl,(C2-C20)alkenyl or —C(═O)—(C1-C20)alkyl group, which comprises:

(i) reacting compound of formula (I)

where R¹ represents azido group; and all other symbols are as definedearlier, with triphenylphosphine/water or H₂—Pd/C, to produce a compoundof formula (I), where R¹ represents NHR⁴, wherein R⁴ represents hydrogenatom and all other symbols are as defined earlier,

(ii) reacting compound of formula (I), where R¹ represents NHR⁴, whereinR⁴ represents hydrogen atom, with thiophosgene or carbon disulfide andchloromethylformate, in the presence of a base to produce a compound offormula (I), where R¹ represents isothiocyanate group; and all symbolsare as defined earlier,

(iii) converting compound of formula (I) where R¹ representsisothiocynate group, to a compound of formula (I), where R¹ representsNHR⁴, wherein R⁴ represents substituted or unsubstituted —C(═S)—OR^(4b),wherein R^(4b) is as defined above and all other symbols are as definedearlier.

The conversion of compound of formula (I), where R¹ represents azido toa compound of formula (I), where R¹ represents NHR⁴, wherein R⁴represents hydrogen atom may be carried out in the presence of gaseoushydrogen and a catalyst such as Ru, Pd, Rh, Pt, Ni on solid beads suchas charcoal, alumina, asbestos and the like. The reduction may beconducted in the presence of a solvent such as dioxane, acetic acid,ethyl acetate, THF, alcohol such as methanol, ethanol, propanol,isopropanol and the like or mixtures thereof. A pressure betweenatmospheric pressure to 60 psi may be used. The reaction may be carriedout at a temperature in the range of 25 to 60° C., preferably in therange of room temperature to 80° C. The duration of the reaction may bein the range of 2 to 48 h, preferably in the range of 5 to 15 h. Thereduction may also be carried out by employing PPh₃ and water.

The compound of formula (I), where R¹ represents NHR⁴, wherein R⁴represents hydrogen atom may be converted to a compound of formula (I)where R¹ represents isothiocyanate group, by using thiophosgene orcarbon disulfide and chloromethylformate in the presence of a base suchas Et₃N, K₂CO₃, NaOH and the like. The reaction may be carried out inthe presence of a solvent such as dichloromethane (CH₂Cl₂),acetonitrile, chloroform (CHCl₃), DMF, THF and the like. The reactionmay be carried at a temperature in the range of 0 to 60° C., preferablyat 0° C. The reaction may be carried out in an inert atmosphere usingargon or any other inert gas. The duration of the reaction may be in therange of 1 to 24 h, preferably 2 to 10 h.

The conversion of compound of formula (I) where R¹ representsisothiocyanate group, to a compound of formula (I), where R¹ representsNHR⁴, wherein R⁴ represents substituted or unsubstituted —C(═S)—OR^(4b),wherein R^(4b) is as defined above, may be carried out by usingrespective alcohol such as methanol, ethanol, propanol, cyclohexanol andthe like, in the absence or presence of a base such as NaH, KH and thelike. The reaction may be carried out in the presence of a solvent suchas THF, toluene, DMF and the like. The reaction may be carried out at atemperature in the range of room temperature to 130° C., preferably atreflux temperature of the solvent used. The duration of the reaction maybe in the range of 6 to 24 h.

Another embodiment of the present invention provides a process for thepreparation of compound of formula (I), where R¹ represents NHR⁴, whereR⁴ represents substituted or unsubstituted groups selected from—C(═S)—NH₂, —C(═S)—NH—(C1-C20)alkyl, —C(═S)—N—((C1-C20)alkyl)₂,—C(═S)—NH—(C2-C20)alkenyl, C(═S)—NH—C(═O)-aryl, —C(═S)—NH-aralkyl,—C(═S)—NH-heteroaralkyl or —C(═S)—N(R′R″), wherein R′ and R″ groupstogether form a substituted or unsubstituted 5 or 6 membered cyclicstructures containing nitrogen and optionally one or two additionalhetero atoms selected from oxygen, nitrogen or sulfur; from a compoundof formula (I) where R¹ represents isothiocyanate group,

where all symbols are as defined earlier.

The compound of formula (I), where R¹ represents NHR⁴, wherein R⁴represents substituted or unsubstituted —C(═S)—NH₂, may be prepared bypassing ammonia gas into a solution of compound of formula (I) where R¹represents isothiocyanate group, in the presence of a solvent such asTHF, toluene, and the like. The reaction may be carried out at atemperature in the range of −10° C. to room temperature, preferably at+10° C. The duration of the reaction may be in the range from 20 min to4 h, preferably 30 min.

The compound of formula (I), where R¹ represents NHR⁴, wherein R⁴represents substituted or unsubstituted groups selected from—C(═S)—NH—(C1-C20)alkyl, —C(═S)—N—((C1-C20)alkyl)₂,—C(═S)—NH—(C2-C20)alkenyl, C(═S)—NH—C(═O)-aryl, —C(═S)—NH-aralkyl,—C(═S)—NH-heteroaralkyl or —C(═S)—N(R′R″), wherein R′ and R″ groupstogether form a substituted or unsubstituted 5 or 6 membered cyclicstructures containing nitrogen and optionally one or two additionalhetero atoms selected from oxygen, nitrogen or sulfur, may be carriedout by treating a compound of formula (I) where R¹ representsisothiocyanate group with appropriate amine such as methylamine,ethylamine, diemthylamine, diethylamine, benzylamine, aniline, proline,morpholine, thiomorpholine, pyridiylmethylamine and the like, in thepresence of a solvent such as THF, DMF, toluene, and the like. Thereaction may be carried out at a temperature in the range of roomtemperature to 140° C., preferably at room temperature to 100° C. Theduration of the reaction may be in the range of 0.5 to 24 h, preferably0.5 to 12 h.

Yet another embodiment of the present invention provides a process forthe preparation of compound of formula (I), where R¹ represents NHR⁴,wherein R⁴ represents substituted or unsubstituted —C(═S)—SR^(4c),wherein R^(4c) represents (C1-C20)alkyl group, from compound of formula(I), where R¹ represents NHR⁴, wherein R⁴ represents hydrogen atom,

where all other symbols are as defined earlier.

The compound of fomula (I), where R¹ represents NHR⁴, wherein R⁴represents substituted or unsubstituted —C(═S)—SR^(4c), wherein R^(4c)is as defined above, may be prepared from compound of formula (I), whereR¹ represents NHR⁴, wherein R⁴ represents hydrogen atom, by using CS₂ inthe presence of a base such as Et₃N, diisopropyl ethylamine, K₂CO₃, NaH,t-BuOK and the like. The reaction may be carried out in the presence ofalkyl halide such as methyliodide, ethylbromide, propylbromide and thelike. The solvent used in the reaction may be selected from ethanol,methanol, isopropanol, THF, diethylether, acetonitrile and the like, ormixtures thereof. The reaction may be carried out at a temperature inthe range of room temperature to 60° C., preferably at room temperature.The duration of the reaction may be in the range of 6 to 24 h.

Another embodiment of the present invention provides a process for thepreparation of compound of formula (I), where R¹ represents NHR⁴,wherein R⁴ represents substituted or unsubstituted —C(═S)—NH—R^(4d),wherein R^(4d) represents —C(═O)-aryl group, from compound of formula(I), where R¹ represents NHR⁴, wherein R⁴ represents hydrogen atom,

where all other symbols are as defined earlier.

The compound of fomula (I), where R¹ represents NHR⁴, wherein R⁴represents substituted or unsubstituted —C(═S)—NH—R^(4d) wherein R^(4d)is as defined above, may be prepared from compound of formula (I), wherewhere R¹ represents NHR⁴, wherein R⁴ represents hydrogen atom by usingbenzoylisothiocyanate. The solvent used in the reaction may be selectedfrom acetone, ethanol, methanol, isopropanol, THF, diethylether,acetonitrile and the like. The temperature of the reaction may bemaintained in the range of 0 to 80° C., preferably in the range of roomtemperature to 60° C. The duration of the reaction may be in the rangeof 1 to 20 h, preferably in the range of 1 to 10 h.

Yet another embodiment of the present invention provides a process forthe preparation of compound of formula (I), where R¹ represents NHR⁴,wherein R⁴ represents substituted or unsubstituted —C(═O)-heteroaryl,from a compound of formula (I), where R¹ represents NHR⁴, wherein R⁴represents hydrogen atom,

where all other symbols are as defined earlier.

The compound of fomula (I), where R¹ represents NHR⁴, wherein R⁴represents substituted or unsubstituted —C(═O)-heteroaryl, may beprepared from compound of formula (I), where R¹ represents NHR⁴, whereinR⁴ represents hydrogen atom by treating with corresponding heteroaroylacid chloride and base such such as pyridine, triethylamine ordiisopropylamine. The reaction may also be carried out by usingcorresponding heteroaryl acid and dicyclohexylcarbodiimide (DCC) in thepresence of DMAP. The solvent used in the reaction may be selected fromacetonitrile, THF, acetonitrile, Et₂O and the like. The temperature ofthe reaction may be maintained in the range of −5 to 100° C., preferablyin the range of 0 to 80° C. The duration of the reaction may be in therange of 1 to 15 h, preferably in the range of 2 to 12 h.

Still another embodiment of the present invention provides a process forthe preparation of compound of formula (I), where R¹ represents NHR⁴where R⁴ represents substituted or unsubstituted —C(═O)—R^(4e) whereinR^(4e) represents (C1-C20)alkyl, (C1-C20)alkoxy, (C2-C20)alkenyl,halo(C1-C20)alkyl, aryl, aryloxy, heteroaryl, (C2-C20)alkenyloxy,(C1-C20)alkylcarbonyl, arylcarbonyl, aryloxycarbonyl,(C1-C20)alkoxycarbonyl, (C1-C20)alkylthiocarbonyl or(C1-C20)arylthiocarbonyl; from a compound of formula (I), where R¹represents NHR⁴, wherein R⁴ represents hydrogen atom,

where all other symbols are as defined earlier.

The compound of formula (I), where R¹ represents NHR⁴, wherein R⁴represents substituted or unsubstituted —C(═O)—R^(4e), wherein R^(4e) isas defined above, may be prepared from compound of formula (I), where R¹represents NHR⁴, wherein R⁴ represents hydrogen atom, by treating withappropriate acid halide such as acetyl chloride, propionyl chloride andthe like; alkylchloroformate like methylchloroformate,ethylchloroformate and the like; aralkylchloroformate likebenzylchloroformate and the like; or anhydride of the corresponding acidsuch as acetic anhydride. The reaction may be carried out in thepresence of a solvent such as CH₂Cl₂, CHCl₃, toluene, THF and the likeor mixtures thereof. The reaction may also be carried out in thepresence of a base like Et₃N, diisopropyl ethylamine, pyridine, K₂CO₃,NaH, potassium tert-butoxide (t-BuOK) and the like. The temperature ofthe reaction may be maintained in the range of −20 to 60° C., preferablyin the range of 0 to room temperature. The duration of the reaction maybe in the range of 1 to 12 h, preferably from 1 to 4 h.

Yet another embodiment of the present invention provides a process forthe preparation of compound of formula (I) where R¹ represents NHR⁴where R⁴ represents substituted or unsubstituted —C(═NH)—NH₂, byreacting a compound of formula (I), where R¹ represents NHR⁴ wherein R⁴represents hydrogen atom, with di-tert-butoxy carbonyl thiourea,

where all other symbols are as defined earlier.

The compound of formula (I) where R¹ represents NHR⁴ where R⁴ representssubstituted or unsubstituted group selected from —C(═NH)—NH₂, may beprepared by reacting the compound of formula (I), where R¹ representsNHR⁴ where R⁴ represents hydrogen atom, with di-tert-butoxy carbonylthiourea in two steps. In the first step, the reaction may be carriedout in the presence of solvents such as DMF, acetone, THF,dichloromethane and the like. The base used in the reaction may beselected from triethylamine, diisopropylethylamine, pyridine and thelike. The temperature of the reaction may be in the range of 0 to 120°C., preferably in the range of 0 to 90° C. The duration of the reactionmay be in the range of 0.2 to 15 h, preferably in the range of 0.5 to 10h. In the second step, the compound obtained in the first step may bereacted with trifluoroacetic acid in the presence of a solvent such asdichloromethane, chloroform, THF and the like. The temperature of thereaction may be in the range of 0 to 110° C., preferably in the range of0 to 90° C. The duration of the reaction may be in the range of 0.5 to60 h, preferably in the range of 0.5 to 54 h.

Another embodiment of the present invention provides an alternativeprocess for the preparation of compound of formula (I) where R¹represents NHR⁴ where R⁴ represents substituted or unsubstituted groupselected from —C(═NH)—NH₂, by reacting a compound of formula (I), whereR¹ represents NHR⁴ wherein R⁴ represents substituted or unsubstitutedgroup selected from —S(O)₂(C1-C20)alkyl or —S(O)₂aryl group, withguanidine hydrochloride,

where all other symbols are as defined earlier.

The compound of formula (I) where R¹ represents NHR⁴ where R⁴ representssubstituted or unsubstituted group selected from —C(═NH)—NH₂, may beprepared by reacting the compound of formula (I), where R¹ representsNHR⁴ wherein R⁴ represents substituted or unsubstituted group selectedfrom —S(O)₂(C1-C20)alkyl or —S(O)₂aryl group, with guanidinehydrochloride. The solvent used in the reaction may be seleceted fromt-butyl alcohol. The base used in the reaction may be selected from NaH,KH, sodium hexamethyldisilazide (Na-HMDS) and the like. The temperatureof the reaction may be in the range of 0° C. to boiling temperature ofthe solvent used. The duration of the reaction may be in the range of 1to 30 h, preferably in the range of 1 to 24 h.

Still another embodiment of the present invention provides a process forthe preparation of compound of formula (I) where R¹ represents NHR⁴where R⁴ represents substituted or unsubstituted group selected from—C(═NH)—(C1-C20)alkyl or —C(═NH)-aryl, which comprises:

(i) reacting the compound of formula (I)

where R¹ repersents NHR⁴, wherein R⁴ represents —C(═S)—NH₂ and all othersymbols are as defined earlier, with di tert-butoxy carbonyl ether((BOC)₂O), to produce a compound of formula (I), where R¹ representsNHR⁴, wherein R⁴ represents —C(═S)—NH₂ group substituted withtert-butoxy carbonyl group and all symbols are as defined earlier and

(ii) reacting the above compound of formula (I), with a compound offormula (Ih)R⁷—NH₂   (Ih)where R⁷ represents substituted or unsubstituted (C1-C20)alkyl or arylgroup, to produce a compound of formula (I) where R¹ represents NHR⁴where R represents substituted or unsubstituted group selected from—C(═NH)—(C1-C20)alkyl or —C(═NH)-aryl group and all other symbols are asdefined earlier.

The conversion of the compound of formula (I) where R¹ represents NHR⁴,wherein R⁴ represents —C(═S)—NH₂, to a compound of formula (I), where R¹represents NHR⁴, wherein R⁴ represents —C(═S)—NH₂ group substituted withtert-butoxy carbonyl group may be carried out by reacting with (BOC)₂O,in the presence of solvent such as THF, diethylether and the like. Thebase used in the reaction may be selected from NaH, KH, Na-HMDS and thelike. The temperature of the reaction may be in the range of 0 toboiling temperature of the solvent. The duration of the reaction may bein the range of 0.5 to 14 h, preferably in the range of 0.5 to 10 h.

The conversion of the compound of formula (I), where R¹ represents NHR⁴,wherein R⁴ represents —C(═S)—NH₂ group substituted with tert-butoxycarbonyl group, to a compound of formula (I) may be carried out byreacting with the compound of formula (Ih) in two steps. In the firststep, the reaction may be carried out in the presence of a solvent suchas DMF, THF, chloroform, dichloromethane and the like. The base used inthe reaction may be selected from triethylamine, diisopropylethylamine,pyridine and the like. The temperature of the reaction may be in therange of 0 to 120° C., preferably in the range of 0 to 90° C. Theduration of the reaction may be in the range of 0.5 to 24 h, preferablyin the range of 0.5 to 20 h. In the second step, the compound obtainedin the first step may be reacted with trifluoroacetic acid in thepresence of a solvent such as dichloromethane, chloroform, THF and thelike. The temperature of the reaction may be in the range of 0 to 110°C., preferably in the range of 0 to 90° C. The duration of the reactionmay be in the range of 0.5 to 60 h, preferably in the range of 0.5 to 54h.

Yet another embodiment of the present invention provides a process forthe preparation of a compound of formula (I) where R¹ representshalogen, from compound of formula (I) where R¹ represents hydroxy group,

where all other symbols are as defined above.

The compound of formula (I) where R¹ represents halogen is prepared fromcompound of formula (I) where R¹ represents hydroxy group may be carriedout by treating with SOCl₂, PCl₅, PBr₃, tetrahalomethane group such asCBr₄, CCl₄ and the like, in the presence of PPh₃, P(alkyl)₃ and thelike. The reaction may be carried out in the presence of a solvent suchas dry dichloromethane, chloroform, tetrachloromethane, benzene, DMF,DMSO, THF and the like. The temperature of the reaction may bemaintained in the range of 0 to 60° C., preferably at room temperature.The duration of the reaction may be in the range of 0.5 to 24 hours,preferably 1 to 13 h.

Still another embodiment of the present invention provides a process forthe preparation of a compound of formula (I) where R¹ represents ‘SH’,

where all other symbols are as defined above, which comprises:

(i) reacting the compound of formula (I) where R¹ represents halogenatom, to produce a compound of formula (Ii),

where all other symbols are as defined earlier, with a base andthiolacetic acid,

(ii) reacting the compound of formula (Ii), to produce a compound offormula (I) where R¹ represents ‘SH’ group and all other symbols are asdefined earlier, with base.

The compound of formula (Ii) is prepared from compound of formula (I)where R¹ represents halogen atom may be prepared by using thiolaceticacid in the presence of a base such as triethylamine, di-isopropylamine,di-isopropylethylamine, pyridine, piperidine, DMAP,1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), lithium diisopropylamide(LDA), potassium bis-(trimethyl silyl)amide, BuLi, Na₂CO₃, K₂CO₃, NaOH,KOH, NaOMe, NaOEt, NaOiPr, t-BuOK, NaH, KH and the like. The solventused in the reaction may be seleceted from THF, benzene, dioxane and thelike. The temperature of the reaction may be maintained in the range ofroom temperature to reflux temperature, preferably at refluxtemperature. The duration of the reaction may be in the range of 2 to 24hours, preferably 6 hours.

The compound of formula (I), where R¹ represents ‘SH’ group may beprepared from a compound of formula (Ii) by reacting with a base such asK₂CO₃, NaOH, KOH, BuLi and the like. The reaction may be carried out ata temperature in the range of room temperature to reflux temprature. Theduration of the reaction may be in the range of 1 to 24 hours.

Still yet another embodiment of the present invention provides a processfor the preparation of compound of formula (I), where R¹ represent NHR⁴wherein R⁴ represents substituted or unsubstituted —S(O)₂(C1-C20)alkylor —S(O)₂aryl group, from a compound of formula (I) where R¹ representsNHR⁴ where R⁴ represents hydrogen atom,

(i) reacting the compound of formula (I),

where R¹ represents NHR⁴ where R⁴ represents hydrogen atom and all othersymbols are as defined in the description, to a compound of formula (I),where R¹ represents NHR⁴, wherein R⁴ represents substituted orunsubstituted group selected from —S(O)₂—(C1-C20)alkyl or —S(O)₂-arylgroup and all other symbols are as defined in the description, to acompound of formula (I).

The conversion of compound of formula (I), where R¹ represents NHR⁴where R⁴ represents hydrogen atom, to a compound of formula (I), whereR¹ represents NHR⁴, wherein R⁴ represents substituted or unsubstitutedgroup selected from —S(O)₂—(C1-C20)alkyl or —S(O)₂-aryl group, may becarried out by treating with alkylsulfonylchloride orarylsulfonylchloride such as methanesulfonyl chloride, p-toluenesulfonylchloride and the like. The solvent used may be selected fromdichloromethane, tetrahydrofuran, acetonitrile, dimethylformamide,dimethylsulfoxide and the like. The temperature of the reaction may bein the range of 0 to 50° C., for a duration of 1 to 6 hours.

Another embodiment of the present invention provides a novelintermediate of the formula (Ie),

where A, B, D, Y¹, Y², R² and R³ are as defined earlier.

Yet another embodiment of the present invention provides a process forthe preparation of novel intermediate of formula (Ie), which comprises:

(i) reacting the compound of formula (Ia)

where X represents halogen atom such as fluorine, chlorine, bromine andthe like; R² and R³ are as defined earlier, with a compound of formula(Ib)

where A, B, D, Y¹ and Y² are as defined earlier, to produce a compoundof formula (Ic)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier,

(ii) reducing the compund of formula (Ic) by using reducing agent to acompound of formula (Id)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier

(iii) converting the compound of formula (Id) to a compound of formula(Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier.

The compound of formula (Ic) may be prepared by reacting a compound offormula (Ia) with a compound of formula (Ib) by using a base such asKOH, NaOH, K₂CO₃, Na₂CO₃, NaH, KH, triethylamine, diisopropylethyl amineand the like. The reaction may be carried out using a solvent such asDMSO, DMF, THF, acetonitrile, chloroform, nitrobenzene and the like ormixtures thereof. The reaction may be carried out in inert atmosphere,which may be maintained using inert gases such as N₂ or Ar. The reactionmay be carried out at a temperature in the range of 20 to 100° C.,preferably at a temperature in the range of ambient −80° C. The reactiontime may range from 1 to 15 hours, preferably from 6 to 12 hours.

The reduction of a compound of formula (Ic) to produce a compound offormula (Id) may be carried out in the presence of reducing agents suchas NiCl₂/NaBH₄, lithium aluminium hydride (LAH), gaseous hydrogen and acatalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such as charcoal,alumina, asbestos and the like. The reduction may be carried out in thepresence of a solvent such as dioxane, acetic acid, ethyl acetate, THF,alcohol such as methanol, ethanol and the like or mixtures thereof. Apressure between atmospheric pressure to 60 psi may be used. Thereaction may be carried out at a temperature from 0 to 60° C.,preferably at 0 to room temperature. The reaction time ranges from 0.5to 48 hours, preferably in the range of 0.5 to 5 hours. The reductionmay also be carried out by employing metal in mineral acids such Sn/HCl,Fe/HCl, Zn/HCl, Zn/CH₃CO₂H and the like.

The compound of formula (Id) may be converted to a compound of formula(Ie) by using NaNO₂ in the presence of HCl or CH₃COOH followed by NaN₃.The solvent used in the reaction may be selected from methanol, ethanol,ethylacetate, THF, ether, dioxan and the like. The temperature of thereaction may be maintained in the range of −40° C. to boilingtemperature, preferably in the range of 0° C. to room temperature. Theduration of the reaction may be in the range of 0.5 to 15 hours,preferably in the range of 0.5 to 5 hours.

Another embodiment of the present invention provides a novelintermediate of the formula (If),

where R^(c) represents substituted or unsubstituted (C1-C20)alkyl groupsuch as methyl, ethyl, n-propyl, iso-propyl and the like; A, B, D, Y¹,Y², R² and R³ are as defined earlier.

Yet another embodiment of the present invention provides a process forthe preparation of novel intermediate of formula (If), which comprises:

(i) reacting the compound of formula (Ia)

where X represents halogen atom such as fluorine, chlorine, bromine andthe like; R² and R³ are as defined earlier, with a compound of formula(Ib)

where A, B, D, Y¹ and Y² are as defined earlier, to produce a compoundof formula (Ic)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier,

(ii) reducing the compund of formula (Ic) by using reducing agent to acompound of formula (Id)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier

(iii) converting the compound of formula (Id) to a compound of formula(Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined earlier

(iv) converting the compound of formula (Ie) to a compound of formula(If)

where R^(c) represents substituted or unsubstituted (C1-C20)alkyl groupsuch as methyl, ethyl, n-propyl, iso-propyl and the like; A, B, D, Y¹,Y² , R² and R³ are as defined earlier.

The compound of formula (Ic) may be prepared by reacting a compound offormula (Ia) with a compound of formula (Ib) by using a base such asKOH, NaOH, K₂CO₃, Na₂CO₃, NaH, KH, triethylamine, diisopropylethyl amineand the like. The reaction may be carried out using a solvent such asDMSO, DMF, THF, acetonitrile, chloroform, nitrobenzene and the like ormixtures thereof. The reaction may be carried out in inert atmosphere,which may be maintained using inert gases such as N₂ or Ar. The reactionmay be carried out at a temperature in the range of 20 to 100° C.,preferably at a temperature in the range of ambient −80° C. The reactiontime may range from 1 to 15 hours, preferably from 6 to 12 hours.

The reduction of a compound of formula (Ic) to produce a compound offormula (Id) may be carried out in the presence of reducing agents suchas NiCl₂/NaBH₄, lithium aluminium hydride (LAH), gaseous hydrogen and acatalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such as charcoal,alumina, asbestos and the like. The reduction may be carried out in thepresence of a solvent such as dioxane, acetic acid, ethyl acetate, THF,alcohol such as methanol, ethanol and the like or mixtures thereof. Apressure between atmospheric pressure to 60 psi may be used. Thereaction may be carried out at a temperature from 0 to 60° C.,preferably at 0 to room temperature. The reaction time ranges from 0.5to 48 hours, preferably in the range of 0.5 to 5 hours. The reductionmay also be carried out by employing metal in mineral acids such Sn/HCl,Fe/HCl, Zn/HCl, Zn/CH₃CO₂H and the like.

The compound of formula (Id) may be converted to a compound of formula(Ie) by using NaNO₂ in the presence of HCl or CH₃COOH followed by NaN₃.The solvent used in the reaction may be selected from methanol, ethanol,ethylacetate, THF, ether, dioxan and the like. The temperature of thereaction may be maintained in the range of −40° C. to boilingtemperature, preferably in the range of 0° C. to room temperature. Theduration of the reaction may be in the range of 0.5 to 15 hours,preferably in the range of 0.5 to 5 hours.

The compound of formula (If) may be prepared by heating a compound offormula (Ie) with esters ((C1-C20)alkyl or aryl). The solvent used inthe reaction may be selected from benzene, toluene, xylene,acetonitrile, THF and the like. The temperature of the reaction may bemaintained in the range of 0 to 200° C., preferably in the range of roomtemperature to boiling temperature of the solvent. The duration of thereaction may be in the range of 2 to 25 hours, preferably 3 to 15 hours.

Another embodiment of the present invention provides a novelintermediate of the formula (Ig),

where all symbols are as defined earlier.

Yet another embodiment of the present invention provides a process forthe preparation of novel intermediate of formula (Ig), which comprises:

(i) converting the compound of formula (If)

where R^(c)represents substituted or unsubstituted (C1-C20)alkyl groupsuch as methyl, ethyl, n-propyl, iso-propyl and the like; A, B, D, Y¹,Y², R² and R³ are as defined earlier, to a compound of formula (Ig)

where all symbols are as defined earlier.

The conversion of compound of formula (If) to a compound of formula (Ig)may be carried out in the presence of ammonia solution in water oralcohol. The temperature of the reaction may be in the range of −40 to50° C., preferably of 0° C. to room temperature. The duration of thereaction may be in the range of 0.5 to 12 hours, preferably 0.5 to 4hours.

Another embodiment of the present invention provides a novelintermediate of the formula (Ij),

where R^(d) represents substituted or unsubstituted groups selected from—(C1-C20)alkyl, —CO₂R^(c), —CH₂OH, —CH₂NH₂, —CH₂N(Pthalimide),—CH₂NH—C(═S)S—O(C1-C20)alkyl or —CH₂NH—C(═O)—(C1-C20)alkyl and all othersymbols are as defined earlier.

The compound of formula (Ij) represents the compounds of formula (I),when R^(d) represents substituted or unsubstituted groups selected from—(C1-C20)alkyl, —CH₂OH, —CH₂NH₂, —CH₂N(Pthalimide),—CH₂NH—C(═S)S—O(C1-C20)allyl, —CH₂NH—C(═O) (C1-C20)alkyl.

Still yet another embodiment of the present invention provides a processfor the preparation of novel intermediate of formula (Ij), whichcomprises:

(i) converting the compound of formula (Ie),

where Z, Y¹, Y², Y³, R² and R³ are as defined earlier, with≡R^(d)   (Ik)where R^(d) is as defined above, to a compound of formula (Ij)

where Z, Y¹, Y², Y³, R^(d), R² and R³ are as defined earlier.

The compound of formula (Ij) may be prepared by reacting the compound offormula (Ie) with a compound of formula (Ik), in the presence of a basesuch as triethylamine, ethyldiisopropylamine, DABCO and the like. Thereaction may be carried out in the presence of a solvent such asdichloromethane, chloroform, tetrahydrofuran, dimethylformamide,dimethylsulfoxide, acetonitrile and the like. The reaction may becarried out in the presence of Cu (I)I.

It is appreciated that in any of the above-mentioned reactions, anyreactive group in the substrate molecule may be protected according toconventional chemical practice. Suitable protecting groups in any of theabove mentioned reactions are tertiarybutyldimethylsilyl, methoxymethyl,triphenyl methyl, benzyloxycarbonyl, tetrahydropyran(THP) etc, toprotect hydroxyl or phenolic hydroxy group; N-tert-butoxycarbonyl(N-Boc), N-benzyloxycarbonyl (N-Cbz), N-9-fluorenyl methoxy carbonyl(—N-FMOC), benzophenoneimine, propargyloxy carbonyl (POC) etc, forprotection of amino or anilino group, acetal protection for aldehyde,ketal protection for ketone and the like. The methods of formation andremoval of such protecting groups are those conventional methodsappropriate to the molecule being protected.

A method of treating or preventing an bacterial infections in a subjectis provided by administering an therapeutically effective amount ofcompound of formula (I).

The term “therapeutically effective amount” shall mean that amount of adrug or pharmaceutical agent that will elicit the biological or medicalresponse of a tissue, system or patient that is being sought.

The pharmaceutically acceptable salts are prepared by reacting thecompounds of formula (I) wherever applicable with 1 to 4 equivalents ofa base such as sodium hydroxide, sodium methoxide, sodium hydride,potassium t-butoxide, calcium hydroxide, magnesium hydroxide and thelike, in the presence of a solvent like ether, THF, methanol, t-butanol,dioxane, isopropanol, ethanol etc. Mixture of solvents may be used.Organic bases like lysine, arginine, diethanolamine, choline,tromethamine, guanidine and their derivatives etc. may also be used.Alternatively, acid addition salts wherever applicable are prepared bytreatment with acids such as hydrochloric acid, hydrobromic acid, nitricacid, sulfuric acid, phosphoric acid, p-toluenesulphonic acid,methanesulfonic acid, acetic acid, citric acid, maleic acid salicylicacid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinicacid, benzoic acid, benzenesulfonic acid, tartaric acid and the like inthe presence of a solvent like ethyl acetate, ether, alcohols, acetone,THF, dioxane etc. Mixture of solvent may also be used. The salts ofamino acid groups and other groups may be prepared by reacting thecompounds of formula (I) with the respective groups in the presence of asolvent like alcohols, ketones, ether etc. Mixture of solvents may beused.

The present invention also provides pharmaceutical compositions,containing compounds of the general formula (I), their pharmaceuticallyacceptable salts The pharmaceutical compositions according to thisinvention can be used for the treatment of bacterial infections. Theycan also be used for the treatment of bacterial infections associatedwith multidrug resistance. The pharmaceutical compositions according tothis invention can also be administered prophylatically for theprevention of bacterial infections in a patient at risk of developing abacterial infection.

The pharmaceutical compositions may be in the forms normally employed,such as tablets, capsules, powders, dispersible granules, cachets,suppositories, syrups, solutions, suspensions and the like, may containflavorants, sweeteners etc. in suitable solid or liquid carriers ordiluents, or in suitable sterile media to form injectable solutions orsuspensions. Such compositions typically contain from 0.5 to 90% byweight of active compound, the remainder of the composition beingpharmaceutically acceptable carriers, diluents or solvents.

Suitable pharmaceutically acceptable carriers include solid fillers ordiluents and sterile aqueous or organic solutions. The active compoundswill be present in such pharmaceutical compositions in the amountssufficient to provide the desired dosage in the range as describedabove. Thus, for oral administration, the compounds can be combined witha suitable solid, liquid carrier or diluent to form capsules, tablets,powders, syrups, solutions, suspensions and the like. The pharmaceuticalcompositions, may, if desired, contain additional components such asflavorants, sweeteners, excipients and the like. For parenteraladministration, the compounds can be combined with sterile aqueous ororganic media to form injectable solutions or suspensions. For example,solutions in sesame or peanut oil, aqueous propylene glycol and the likecan be used, as well as aqueous solutions of water-solublepharmaceutically-acceptable acid addition salts or salts with base ofthe compounds. The injectable solutions prepared in this manner can thenbe administered intravenously, intraperitoneally, subcutaneously, orintramuscularly, with intramuscular administration being preferred inhumans.

The compounds of the formula (I) or pharmaceutical compositions thereofas defined above are clinically administered to mammals, including humanbeings, via oral, parenteral and/or topical routes. Administration bythe oral route is preferred, being more convenient and avoiding thepossible pain and irritation of injection. However, in circumstanceswhere the patient cannot swallow the medication, or absorption followingoral administration is impaired, as by disease or other abnormality, itis essential that the drug be administered parenterally. By eitherroute, the dosage is in the range of about 0.1 mg/kg to about 100 mg/kg,more preferably about 3.0 mg/kg to about 50 mg/kg of body weight of thesubject per day administered singly or as a divided dose. However, theoptimum dosage whether for prevention or treatment for the individualsubject being treated will be determined by the person responsible fortreatment, Initial dosage may be smaller than the optimum and the dailydosage may be progressively increased during the course of treatmentdepending on the particular situation. If desired, the daily dose mayalso be divided into multiple doses for administering, e.g. 2-4 timesper day. It is to be understood that the dosages may vary depending uponthe requirements of the patient, the severity of the bacterial infectionbeing treated, and the particular compound being used. In a topicaltreatment an effective amount of compound of formula (I) is admixed in apharmaceutically acceptable gel or cream vehicle that can be applied tothe patient's skin at the area of treatment. Such creams and gels can beprepared by the procedures available in the literature and can includepenetration enhancers.

The manner in which the compounds of this invention can be prepared isillustrated in the following examples, which demonstrate the preparationof typical species of the invention. In these examples, the identitiesof compounds, intermediates and final, were confirmed by infrared,nuclear magnetic spectral analyses as necessary. The examples are forthe purpose of illustration only and should not be regarded as limitingthe invention in any way.

Preparation 1

1-Azido-4-nitrobenzene

To a solution of p-nitroaniline (5.00 g, 36.2 mmol) in 6N HCl (150 mL),cooled to 0° C., was added sodium nitrite (4.99 g, 72.4 mmol) andstirred at the same temperature for 0.5 hours. A saturated solution ofsodium azide (4.70 g, 72.4 mmol) and sodium acetate (59 g, 724 mmol) inwater (200 mL) was added dropwise to the above reaction mixture over aperiod of 0.5 hours. The precipitate formed was filtered and washedrepeatedly with water and dried under vacuum. The title azide wasobtained as a brown solid (5.60 g, 95%).

¹H NMR (CDCl₃): δ 8.25 (d, J=9.3 Hz, 2H), 7.15 (d, J=9.3 Hz, 2H).

MS (m/e): 165 (M⁺+1), 139, 117.

Preparation 2

[1-(4-Nitrophenyl)-1H-[1,2,3]triazol-4-yl]-methanol &[1-(4-nitrophenyl)-1H-[1,2,3]triazol-5-yl]-methanol

Propargyl alcohol (8.19 g, 146.3 mmol) was added to a solution of1-azido-4-nitrobenzene (8.00 g, 48.8 mmol), obtained in preparation 1,in toluene (200 mL) and refluxed for 15 hours. Toluene was removed undervacuum on rotavapor to yield the title compounds (mixture ofregioisomers) as light brown solid (9.70 g, 90%).

MS (m/e): 221 (M⁺+1).

Preparation 3:

Methanesulfonic acid [1-(4-nitrophenyl)-1H-[1,2,3]triazol-4-yl]-methylester & methanesulfonic acid[1-(4-nitrophenyl)-1H-[1,2,3]triazol-5-yl]-methyl ester

To an ice cooled solution containing a mixture of[1-(4-nitrophenyl)-1H-[1,2,3]triazol-4-yl]-methanol and[1-(4-nitrophenyl)-1H-[1,2,3]triazol-5-yl]-methanol (9.70 g, 44 mmol),obtained in preparation 2, in DMF (50 mL), was added triethylamine(11.47 g, 113.6 mmol) followed by the addition of methanesulfonylchloride (7.77 g, 68.17 mmol) and the reaction mixture was stirred atthe same temperature for 4 hours. The reaction mixture was diluted withcold water (100 mL) and extracted with ethyl acetate (100 mL×3). Thecombined ethyl acetate extracts were washed with water followed by brineand dried over sodium sulfate. Evaporation of volatiles on rotavaporyielded the title compounds (mixture of regioisomers) as yellow oil (10g, 76%).

Preparation 4:

4-Azidomethyl-1-(4-nitrophenyl)-1H-[1,2,3] triazole

Sodium azide (4.92 g, 75.8 mmol) was added to a solution containing amixture of methanesulfonic acid[1-(4-nitrophenyl)-1H-[1,2,3]triazol-4-yl]-methyl ester &methanesulfonic acid [1-(4-nitrophenyl)-1H-[1,2,3]triazol-5-yl]-methylester (10 g, 37.8 mmol), obtained in preparation 3, in DMF (50 mL) andthe reaction mixture was heated to 90° C. for 1 h. The reaction mixturewas then cooled to room temperature and diluted with ethyl acetate (250mL). The organic layer was washed with water followed by brine and driedover sodium sulfate. Removal of volatiles on rotavapor and purificationof the resulting residue by column chromatography (silica gel) yieldedthe title compound as yellow solid (3.60 g, 44%).

¹H NMR (CDCl₃): δ 8.45 (d, J=8.8 Hz, 2H), 8.16 (s, 1H), 7.99 (d, J=8.8Hz, 2H), 4.60 (s, 2H); MS (m/e): 246 (M⁺+1)

Preparation 5:

C-[1-(4-Nitrophenyl)-1H-[1,2,3]triazol-4-yl]-methylamine

A mixture of 4-azidomethyl-1-(4-nitrophenyl)-1H-[1,2,3]triazole (3.60 g,14.7 mmol), obtained in preparation 4, and triphenylphosphine (4.23 g,16 mmol) in THF (50 mL) was stirred at room temperature for 4 hours. Itwas then warmed to 40° C. after the addition of 5 mL of water andallowed to stir at the same temperature for 16 hours. The reactionmixture was then diluted with water and extracted with ethyl acetate(100 mL×2). Combined ethyl acetate extracts were washed with waterfollowed by brine and dried over sodium sulfate. Evaporation ofvolatiles and purification of the resulting residue by columnchromatography (silica gel, CHCl₃/MeOH, 9:1) yielded the title amine (1g, 32%).

¹H NMR (CDCl₃): δ 8.42 (d, J=9.3 Hz, 2H), 8.00 (d, J=9.3 Hz, 2H), 7.83(s, 1H), 4.01 (s, 2H); MS (m/e): 220 (M⁺+1), 190;

Preparation 6:

[1-(4-Nitrophenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamic acidO-methyl ester

To an ice-cooled solution ofC-[1-(4-nitrophenyl)-1H-[1,2,3]triazol-4-yl]-methylamine (1 g, 4.5mmol), obtained in preparation 5, in chloroform (40 mL) was added asaturated solution of sodium bicarbonate followed by the addition ofthiophosgene (0.63 grams, 5.5 mmol) and stirred at room temperature for0.5 hours. The reaction mixture was then diluted with ethyl acetate (100mL) and the organic layer was washed with water followed by brine anddried over sodium sulfate. Evaporation of volatiles left a residue,which was refluxed with methanol (30 mL) for 16 hours. Removal ofmethanol on rotavapor and purification of the resulting residue througha silica gel column (ethyl acetate/chloroform, 1:9) yielded the titlecompound as white solid (800 mg, 70%).

¹H NMR (CDCl₃+DMSO-d₆): δ 9.05 (bs, 1H), 8.41 (d, J=8.9 Hz, 2H), 8.00(d, J=8.9 Hz, 2H), 4.91 & 4.65 (2 d, J=5.9 Hz, 2H, rotamers in a ratioof 4:1), 4.12 & 4.09 (2 s, 3H, rotamers in a ratio of 1:4); MS (m/e):294 (M⁺+1), 262, 175.

Preparation 7:

[1-(4-Aminophenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamic acidO-methyl ester

A solution of[1-(4-nitrophenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamic acidO-methyl ester (800 mg, 2.73 mmol), obtained in preparation 6, inethanol (10 mL) was added to a warm solution of ammonium chloride (1.46grams, 27.30 mmol) in ethanol (30 mL) and water (15 mL). Iron powder(0.45 grams, 8.19 mmol) was added slowly in portion to the reactionmixture over a period of 0.5 hours and stirred for another 0.5 hours at95° C. The reaction mixture was then filtered to remove the blackmaterial and diluted with ethyl acetate (100 mL). The organic phase waswashed with water followed by brine and dried over sodium sulfate.Evaporation of volatiles on rotavapor yielded the title compound aswhite solid (600 mg, 84%).

¹H NMR (CDCl₃+DMSO-d₆): δ 9.22 (bs, 1H), D₂O exchangeable)), 8.12 & 8.09(2s, 1H, rotamers in a ratio of 4:1), 7.41 (d, J=8.6 Hz, 2H), 6.74 (d,J=8.6 Hz, 2H), 4.82 & 4.79 (2d, J=5.9 Hz, 2H, rotamers in a ratio of4:1), 4.03 & 3.95 (2s, 3H, rotamers in a ratio of 1:4); MS (m/e): 264(M⁺+1), 232, 145.

Preparation 8:

2-(2-Fluoro-4-nitro-phenyl)-isoindole-1,3-dione

To a solution of 3,4-difluoronitrobenzene (10 grams, 62.8 mmol) in DMF(25 mL) was added potassium pthalimide (9.18 grams, 62.8 mmol) andheated to 100° C for 4 hours. The reaction mixture was then poured ontocrushed ice and the resulting solid was filtered. The precipitate waswashed with water and dried under vacuum to get the title compound ascrystalline yellow solid.

¹H NMR (DMSO-d₆): δ 8.41 (d, J=9.7 Hz, 1H), 8.31 (d, J=8.9 Hz, 1H),8.08-7.90 (m, 5H); MS (m/e): 287 (M⁺+1); IR (KBr, cm⁻¹): 1737, 1718,1521, 1510, 1377.

Preparation 9:

2-(4-Amino-2-fluoro-phenyl)-isoindole-1,3-dione

To a solution of 2-(2-fluoro-4-nitro-phenyl)-isoindole-1,3-dione (3.80grams, 13.6 mmol), obtained in preparation 8, in methanol (15 mL) andTHF (15 mL) was added ammonium formate (6.80 grams, 108.6 mmol) at 0° C.Palladium on charcoal (10%, 500 mg) was added and stirred for 1 hours atroom temperature. Filtration over a pad of celite followed byevaporation of filtrate left a pasty mass, which was diluted with waterand extracted with ethyl acetate (150 mL×2). The combined ethyl acetateextracts were washed with water followed by brine and dried over sodiumsulfate. Evaporation of volatiles on a rotavapor yielded the titlecompound as dark brown solid (2.85 grams, 86%).

¹H NMR (CDCl₃): δ 7.96-7.76 (m, 4H), 7.08 (t, J=8.2 Hz, 2H), 6.53 (d,J=10.2 Hz, 2H); MS (m/e): 257 (M⁺+1), 237, 148, 127; IR (KBr, cm⁻¹):1706, 1634, 1522, 1397.

Preparation 10:

2-(4-Azido-2-fluoro-phenyl)-isoindole-1,3-dione

To an ice cooled solution of2-(4-amino-2-fluorophenyl)-isoindole-1,3-dione (500 mg, 2 mmol),obtained in preparation 9, in 6N HCl (15 mL) was added sodium nitriteand stirred for 1 hours. A solution of sodium azide (65 mg, 1 mmol) andsodium acetate (3.28 grams, 20 mmol) in water (50 mL) was added andstirred for few min. The reaction mixture was then extracted with ethylacetate (50 mL×2). The combined organic layer was washed with waterfollowed by brine and dried over sodium sulfate. Evaporation ofvolatiles yielded the title compound as brown solid (518 mg, 92%).

¹H NMR (CDCl₃): δ 7.99-7.95 (m, 2H), 7.90-7.79 (m, 2H), 7.35 (t, J=8.3Hz, 1H), 6.99-6.93 (m, 2H); MS (m/e): 283 (M⁺+1), 254, 148; IR (KBr,cm⁻¹): 2113, 1716, and 1515.

Preparation 11:

4-Azido-2-fluoro-phenylamine

To a solution of 2-(4-azido-2-fluoro-phenyl)-isoindole-1,3-dione (500mg, 1.77 mmol), obtained in preparation 10, in methanol (10 mL) wasadded hydrazine hydrate (532 mg, 10.3 mmol) and refluxed for 2 hours.Evaporation of methanol on rotavapor and purification of the resultingresidue through silica gel column (ethyl acetate/pet. ether, 1:5)yielded the title compound (198 mg, 74%).

¹H NMR (CDCl₃): δ 6.81-6.63 (m, 3H), 3.67 (bs, 2H); MS (m/e): 153(M⁺+1); IR (neat, cm⁻¹): 2114, 1681, 1500.

Preparation 12:

1-(4-Azido-2-fluorophenyl)-1H-pyrrole

To a solution of 4-azido-2-fluoro-phenylamine (100 mg, 0.66 mmol),obtained in preparation 11, in glacial acetic acid (2 mL) was added2,4-dimethoxytetrahydrofuran (87 mg, 0.66 mmol) and heated to 114° C.for 4 hours. The reaction mixture was then treated with saturated sodiumbicarbonate solution and extracted with ethyl acetate (50 mL×2).Combined ethyl acetate extracts were washed with water followed by brineand dried over sodium sulfate. Evaporation of volatiles yielded thetitle compound as dark brown semi solid (98 mg, 74%).

¹H NMR (CDCl₃): δ 7.37 (t, J=8.5 Hz, 1H), 6.87-6.58 (m, 4H), 6.35-6.34(m, 2H); MS (m/e): 203 (M⁺+1), 177; IR (KBr, cm⁻¹): 2113, 1591, 1519,1305.

Preparation 13:

1-(4-Azido-2-fluoro-phenyl)-1H-pyrrole-3-carboxaldehyde

To a solution of 4-azido-2-fluoro-phenylamine (100 mg, 0.66 mmol),obtained in preparation 11, in glacial acetic acid (2 mL) was added2,5-dimethoxy tetrahydrofuran-3-carboxaldehyde (95.6 mg, 0.72 mmol) andheated to 110° C. for 3 hours. The reaction mixture was diluted withwater (25 mL) and neutralized with saturated solution of sodiumbicarbonate. The aqueous layer was then extracted with ethyl acetate (50mL×3) and the combined extracts were washed with water followed bybrine. After drying over sodium sulfate, ethyl acetate was removed onrotavapor and the resulting residue was purified by passing through asilica gel column (ethyl acetate/pet ether, 1:2) to yield the titlecompound as light brown solid (135 mg, 89%).

¹H NMR (CDCl₃): δ 9.85 (s, 1H) 7.58 (s, 1H), 7.40 (t, J=8.3, 2H),6.97-6.74 (m, 3H); MS (m/e): 231 (M⁺+1), 205; IR (neat, cm⁻¹): 2115,1674, 1522.

Preparation 14:

1-(4-Azido-2-fluoro-phenyl)-1H-pyrrole-3-carboxaldehyde oxime

To a solution of 1-(4-azido-2-fluoro-phenyl)-1H-pyrrole-3-carboxaldehyde(135 mg, 0.59 mmol), obtained in preparation 13, in a mixture ofdichloromethane/methanol (1:1, 3 mL) was added hydroxylaminehydrochloride (61.2 mg, 0.88 mmol) followed by the addition of potassiumcarbonate (80.5 mg, 0.58 mmol). The reaction mixture was stirred at roomtemperature for 4 hours. It was then diluted with 50 mL of water andextracted with ethyl acetate (75 mL×3). Combined ethyl acetate extractswere washed with brine and dried over sodium sulfate. Evaporation ofvolatiles in a rotavapor yielded the title compound (130 mg, 90%).

¹H NMR (CDCl₃): δ 8.11 (s, 1H), 7.78 (s, 1H), 7.42-7.28 (m, 2H),6.98-6.81 (m, 3H), 6.64 (bs, 1H); MS (m/e): 247 (M⁺), 246, 228, 217,202; IR (KBr, cm⁻¹): 3216, 2116, 1590, 1520, 1307, 1218, 758.

Preparation 15:

1-(4-Azido-2-fluoro-phenyl)-1H-pyrrole-3-carbonitrile

To a solution of 1-(4-azido-2-fluoro-phenyl)-1H-pyrrole-3-carboxaldehydeoxime (200 mg, 0.82 mmol), obtained in preparation 14, in THF (4 mL) wasadded Burgess reagent [(Methoxycarbonylsulfamoyl)triethylammoniumhydroxide, inner salt, 293 mg, 1.23 mmol] and refluxed at 65° C. for 4hours. It was then concentrated on a rotavapor to get a crude product,which was purified by silica gel column chromatography with a mobilephase petether:ethylacetate (1:1) to get the title compound (81 mg,44%).

¹H NMR (CDCl₃): 7.42-7.31 (m, 2H), 6.54 (d, J=9.4 Hz, 3H), 6.59 (s, 1H);MS (m/e):228 (M⁺+1), 202; IR (neat, cm⁻¹): 3440, 2923, 2133, 1522.

Preparation 16:

2-(2,6-Difluoro-4-nitrophenyl)-isoindole-1,3-dione

To a solution of 3,4,5-trifluoronitrobenzene (10 grams, 56.5 mmol) inDMF (50 mL) was added potassium pthalimide (8.247 grams, 56.5 mmol) andheated to 100° C. for 4 h. The reaction mixture was then poured ontocrushed ice and the resulting solid was filtered. The precipitate waswashed with water and dried under vacuum to get the compound ascrystalline yellow solid (10 grams, 61%).

¹H NMR (CDCl₃): δ 8.11-7.92 (m, 4H), 7.90-7.81 (m, 2H); MS (m/e):305(M⁺+1), 275, 148; IR (KBr, cm⁻¹): 3095, 1742, 1718, 1532, 1510, 1371,1346.

Preparation 17:

2-(4-Amino-2,6-difluorophenyl)-isoindole-1,3-dione

To a solution of 2-(2,6-difluoro-4-nitrophenyl)-isoindole-1,3-dione (10g, 32.89 mmol), obtained in preparation 16, in methanol (45 mL) and THF(15 mL) was added palladium on charcoal (10%, 1.82 grams) and stirredfor 4 hours at room temperature. The reaction mixture was filtered toget rid off the catalyst. Evaporation of volatiles in a rotavaporyielded the title compound as dark brown solid (8.77 grams, 97%).

¹H NMR (CDCl₃+DMSO-d₆): δ 8.01-7.81 (m, 4H), 6.67 (d, J=9.3 Hz, 2H),4.92 (bs, 2H); MS (m/e): 275 (M⁺+1), 230, 148; IR (KBr, cm⁻¹): 3423,3315, 2925, 1714, 1524.

Preparation 18:

2-(4-Azido-2,6-difluorophenyl)-isoindole-1,3-dione

To an ice cooled solution of2-(4-amino-2,6-difluorophenyl)-isoindole-1,3-dione (500 mg, 1.82 mmol),obtained in preparation 17, in 6N HCl (10 mL) was added sodium nitriteand stirred for 4 hours. A solution of sodium azide (136.8 mg, 1.82mmol) and sodium acetate (2.99 grams, 36.49 mmol) in water (100 mL) wasadded and stirred for few min. The reaction mixture was then extractedwith ethyl acetate (50 mL×2). The combined organic layer was washed withwater followed by brine and dried over sodium sulfate. Evaporation ofvolatiles yielded the title compound as brown solid (82 mg, 15%).

¹H NMR (CDCl₃): δ 8.05-7.96 (m, 2H), 7.95-7.73 (m, 2H), 6.78 (d, J=8.1Hz, 2H); MS (m/e): 301 (M⁺+1), 275, 272, 253, 104; IR (KBr, cm⁻¹): 2119,1740, 1716, 1518.

Preparation 19:

4-Azido-2,6-difluoro-phenylamine

To a solution of 2-(4-azido-2,6-difluoro-phenyl)-isoindole-1,3-dione(1.5 grams, 1.53 mmol), obtained in preparation 18, in methanol (10 mL)was added ethylene diamine (1.5 grams, 25 mmol) and stirred at roomtemperature. Evaporation of methanol on rotavapor and purification ofthe resulting residue through silica gel column (ethyl acetate/pet.ether: 1:5) yielded the title compound (707 mg, 83%).

¹H NMR (CDCl₃): δ 6.58 (d, J=6.8 Hz, 2H), 3.66 (bs, 2H); MS (m/e): 171(M⁺+1), 143, 128; IR (neat, cm⁻¹): 3419, 3322, 2118, 1600, 1519.

Preparation 20:

1-(4-Azido-2,6-difluoro-phenyl)-1H-pyrrole-3-carboxaldehyde

To a solution of 4-azido-2,6-difluoro-phenylamine (180 mg, 0.6 mmol),obtained in preparation 19, in glacial acetic acid (2 mL) was added2,5-dimethoxy tetrahydrofuran-3-carboxaldehyde (199 mg, 1.48 mmol) andheated to 100° C. for 4 hours. The reaction mixture was diluted withwater (25 mL) and neutralized with saturated solution of sodiumbicarbonate. The aqueous layer was then extracted with ethyl acetate (50mL×3) and the combined extracts were washed with water followed bybrine. After drying over sodium sulfate, ethyl acetate was removed onrotavapor and the resulting residue was purified by passing through asilica gel column (ethyl acetate/pet ether, 1:2) to yield the titlecompound as light brown solid (296 mg, 80%).

¹HNMR (CDCl₃): δ 9.87 (s, 1H), 7.47 (s, 1H), 6.95-6.75 (m, 4H); MS(m/e): 249 (M⁺+1), 220; IR (KBr, cm⁻¹): 2924, 2118, 1679, 1529.

Preparation 21:

1-(4-Azido-2,6-difluoro-phenyl)-1H-pyrrole-3-carboxaldehyde oxime

To a solution of1-(4-azido-2,6-difluoro-phenyl)-1H-pyrrole-3-carboxaldehyde (456 mg,1.83 mmol), obtained in preparation 20, in a mixture ofdichloromethane/methanol (1:1, 3 mL) was added hydroxylaminehydrochloride (190 mg, 2.74 mmol) followed by the addition of potassiumcarbonate (252 mg, 1.83 mmol). The reaction mixture was stirred at roomtemperature for 4 hours. It was then diluted with 50 mL of water andextracted with ethyl acetate (75 mL×3). Combined ethyl acetate extractswere washed with brine and dried over sodium sulfate. Evaporation ofvolatiles in a rotavapor yielded the title compound (323 mg, 67%).

¹HNMR (CDCl₃): δ 8.11 (s, 1H), 7.68 (s, 1H), 7.06 (s, 1H), 6.91-6.58 (m,4H); MS (m/e): 264 (M⁺+1), 246, 236, 218; IR (neat, cm⁻¹): 3216, 2926,2117, 1527, 1238, 1044.

Preparation 22:

1-(4-Azido-2,6-difluoro-phenyl)-1H-pyrrole-3-carbonitrile

To a solution of1-(4-azido-2,6-difluoro-phenyl)-1H-pyrrole-3-carboxaldehyde oxime (323mg, 1.22 mmol), obtained in preparation 21, in THF (3 mL) was addedBurgess reagent [(Methoxycarbonylsulfamoyl)triethylammonium hydroxide,inner salt, 314 mg, 1.32 mmol] and refluxed at 65° C. for 4 hours. Itwas then concentrated on a rotavapor to get a crude product, which waspurified by silica gel column chromatography with a mobile phasepetether:ethylacetate (1:4) to get the title compound (166 mg, 55%).

¹HNMR (CDCl₃): δ 7.38-7.22 (m, 2H), 6.90-6.71 (m, 2H), 6.63 (s, 1H); MS(m/e): 246 (M⁺+1), 220, 162, 151.

Preparation 23:

1-(2,6-Difluoro-4-nitrophenyl)-1H-imidazole

To a suspension of anhydrous potassium carbonate (17.30 grams, 112.80mmol) in dry DMF (100 mL) was added 3,4,5-trifluoronitrobenzene (10grams, 56.40 mmol) followed by the addition of imidazole (4.60 grams,67.6 mmol) and heated to 80° C. for 1 hours. The reaction mixture wasthen poured onto crushed ice and the resulting solid was filtered. Thesolid collected was washed with water and dried to yield the titlecompound as yellow powder (8 grams, 62%).

¹H NMR (CDCl₃): δ 8.03 (d, J=7.5 Hz, 2H), 7.80 (s, 1H), 7.31 (s, 2H); MS(m/e): 226 (M⁺+1), 196; IR (1KBr, cm⁻¹): 3128, 3027, 1520, 1045.

Preparation 24:

3,5-Difluoro-4-imidazol-1-yl-phenylamine

To a mixture of nickel chloride hexahydrate (16.49 grams, 71.10 mmol)and 1-(2,6-difluoro-4-nitrophenyl)-1H-imidazole (8 grams, 35.50 mmol),obtained in preparation 23, in methanol (100 mL) was added sodiumborohydride (4 grams, 106.60 mmol) in portion and stirred for 0.5 hours.The reaction mixture was diluted with ethyl acetate (500 mL). Theorganic layer was washed with water followed by brine and dried oversodium sulfate. Evaporation of volatiles yielded the title compound asbrown solid (5.90 grams, 85%).

¹H NMR (CDCl₃): δ 7.76 (s, 1H), 7.29 (s, 1H), 7.01 (s, 1H), 6.37 (d,J=10.7 Hz, 2H), 6.02 (bs, 2H); MS (m/e): 196 (M⁺+1); IR (KBr, cm⁻¹):3423, 3339, 3221, 1647.

Preparation 25:

1-(4-Azido-2,6-difluorophenyl)-1H-imidazole

To an ice cooled solution of 3,5-difluoro-4-imidazol-1-yl-phenylamine (1grams, 5.12 mmol), obtained in preparation 24, in 6N HCl (20 mL), wasadded sodium nitrite (0.70 grams, 10.25 mmol) and stirred for 1 hours.Then a saturated solution of sodium azide (0.66 grams, 10.25 mmol) andsodium acetate (8.60 grams, 102.50 mmol) in water (50 mL) was addedslowly at the same temperature. The reaction mixture was diluted withethyl acetate (250 mL). The organic layer was washed with water followedby brine and dried over sodium sulfate. Evaporation of volatiles yieldedthe title compound as light brown solid (1 grams, 90%).

¹H NMR (CDCl₃): δ 7.90 (s, 1H), 7.46 (s, 1H), 7.32 (d, J=8.6 Hz, 2H),7.11 (s, 1H); MS (m/e): 222 (M⁺+1), 196; IR (KBr, cm⁻¹): 2126.

Preparation 26:

1-(2-Fluoro-4-nitrophenyl)-1H-imidazole

To a suspension of anhydrous potassium carbonate (2.60 grams, 15.6 mmol)in dry DMF (15 mL) was added 3,4-difluoronitrobenzene (2.0 grams, 12.6mmol) followed by the addition of imidazole (1.03 grams, 15.1 mmol) andheated to 80° C. for 1 hours. The reaction mixture was then poured ontocrushed ice and the resulting solid was filtered. The solid collectedwas washed with water and dried to yield the title compound as yellowpowder (2 grams, 74%).

¹H NMR (CDCl₃): δ 8.15 (d, J=8.8 Hz, 2H), 7.90 (s, 1H), 7.59 (t, J=8.2Hz, 1H), 7.27 (d, J=4.8 Hz, 2H); MS (m/e): 208 (M⁺+1), 194, 178.

Preparation 27:

3-Fluoro-4-imidazol-1-yl-phenylamine

To a mixture of nickel chloride hexahydrate (4.83 grams, 19.3 mmol) and1-(2-fluoro-4-nitrophenyl)-1H-imidazole (2 grams, 9.7 mmol), obtained inpreparation 26, in methanol (10 mL) was added sodium borohydride (1.1grams, 29.0 mmol) in portion and stirred for 0.5 hours. The reactionmixture was diluted with ethyl acetate (100 mL). The organic layer waswashed with water followed by brine and dried over sodium sulfate.Evaporation of volatiles yielded the title compound as brown oil (1.5grams, 88%).

¹H NMR (CDCl₃): δ 7.79 (s, 1H), 7.38 (t, J=8.1 Hz, 1H), 7.23 (s, 2H),6.97-6.92 (m, 2H); MS (m/e): 178 (M⁺+1), 176.

Preparation 28:

1-(4-Azido-2-fluorophenyl)-1H-imidazole

To an ice cooled solution of 3-fluoro-4-imidazol-1-yl-phenylamine (2.0grams, 11.3 mmol), obtained in preparation 27, in 6N HCl (10 mL), wasadded sodium nitrite (1.5 grams, 22 mmol) and stirred for 1 hours. Thena saturated solution of sodium azide (1.4 grams, 22 mmol) and sodiumacetate (18.5 grams, 226 mmol) in water (50 mL) was added slowly at thesame temperature. The reaction mixture was diluted with ethyl acetate(100 mL). The organic layer was washed with water followed by brine anddried over sodium sulfate. Evaporation of volatiles yielded the titlecompound as light brown solid (2 grams, 83%).

¹H NMR (CDCl₃): δ 7.80 (s, 1H), 7.38 (t, J=8.1 Hz, 1H), 7.20 (s, 2H),6.97-6.92 (m, 2H); MS (m/e): 204 (M⁺+1), 178, 176; IR (KBr, cm⁻¹): 2114.

Preparation 29:

1-(2-Fluoro-4-nitrophenyl)-1H-pyrazole

To a suspension of anhydrous potassium carbonate (4.30 grams, 31.10mmol) in DMF (20 mL) was added 3,4-difluoronitrobenzene (2.50 grams,15.70 mmol) followed by the addition of pyrazole (1.28 grams, 18.80mmol) and heated to 80° C. for 1 hours. The reaction mixture was pouredonto crushed ice and the precipitate was filtered off. It was thenwashed with water and dried under vacuum to yield the title compound asyellow solid (3.00 grams, 86%).

¹H NMR (DMSO-d₆): δ 8.53-8.25 (m, 4H), 7.94 (s, 1H), 6.69 (s, 1H); MS(m/e): 208 (M⁺+1); IR (KBr, cm⁻¹): 3441, 3146, 2925, 2119, 1341.

Preparation 30:

3-Fluoro-4-pyrazol-1-yl-phenylamine

To a mixture of nickel chloride hexahydrate (6.70 grams, 28.80 mmol) and1-(2-fluoro-4-nitrophenyl)-1H-pyrazole (3.00 grams, 14.49 mmol),obtained in preparation 29, in methanol (50 mL) was added sodiumborohydride (1.65 grams, 43.40 mmol) in portion and stirred for 0.5hours. The reaction mixture was diluted with ethyl acetate (500 mL) andthe organic layer was washed with water followed by brine and dried oversodium sulfate. Evaporation of volatiles yielded the title compound asbrown solid (2.30 grams, 90%).

¹H NMR (CDCl₃): δ 7.81 (s, 1H), 7.79 (s, 1H), 7.55 (t, J=8.6 Hz, 1H),6.67-6.42 (m, 3H), 3.80 (bs, 2H); MS (m/e): 178 (M⁺+1); IR (neat, cm⁻¹):3351, 1633, 1532.

Preparation 31:

1-(4-Azido-2-fluoro-phenyl)-1H-pyrazole

Sodium nitrite (1.79 grams, 25.80 mmol) was slowly added to an icecooled solution of 3-fluoro-4-pyrazol-1-yl-phenylamine (2.30 grams,12.90 mmol), obtained in preparation 30, in 6N HCl (20 mL), and stirredfor 1 hours. Then a saturated solution of sodium azide (1.68 grams,25.80 mmol) and sodium acetate (21.80 grams, 258 mmol) in water (90 mL)was added slowly at the same temperature. The reaction mixture wasdiluted with ethyl acetate (500 mL). The organic layer was washed withwater followed by brine and dried over sodium sulfate. Evaporation ofvolatiles yielded the title compound as brown viscous oil (2.20 grams,84%).

¹H NMR (CDCl₃): δ 8.05-7.81 (m, 2H), 7.76 (s, 1H), 7.09-6.82 (m, 2H),6.55 (s, 1H); MS (m/e): 204 (M⁺+1), 167; IR (KBr, cm⁻¹): 2115.

Preparation 32:

[1-(3-Fluoro-4-pyrazol-1-ylphenyl)-1H-[1,2,3]triazol-4-yl]-methanol &[1-(3-fluoro-4-pyrazol-1-ylphenyl)-1H-1,2,3]triazol-5-yl]-methanol

Propargyl alcohol (1.24 grams, 22.10 mmol) was added to a solution of1-(4-azido-2-fluoro-phenyl)-1H-pyrazole (1.50 grams, 7.38 mmol),obtained in preparation 31, in toluene (50 mL) and refluxed for 16hours. Removal of toluene under vacuum on rotavapor yielded a mixture ofregioisomers as viscous liquid (1.60 grams, 85%).

Preparation 33:

Methanesulfonic acid[1-(3-fluoro-4-pyrazol-1-ylphenyl)-1H-[1,2,3]triazol-4-yl]-methyl ester& methanesulfonic acid[1-[3-fluoro-4-pyrazol-1-ylphenyl]-1H-[1,2,3]triazol-5-yl]-methyl ester

Triethyl amine (1.24 grams, 12.20 mmol) was added to a solution of[1-(3-fluoro-4-pyrazol-1-ylphenyl)-1H-[1,2,3]triazol-4-yl]-methanol &[1-(3-fluoro-4-pyrazol-1-ylphenyl)-1H-[1,2,3]triazol-5-yl]-methanol(1.60 grams, 6.17 mmol), obtained in preparation 32, in dichoromethane(30 mL) followed by the addition of methanesulfonyl chloride (1.05grams, 9.20 mmol) at 0° C. and stirred for 1 hours. The reaction mixturewas diluted with dichloromethane (250 mL). The organic layer was washedwith water followed by brine and dried over sodium sulfate. Evaporationof volatiles yielded the title compounds as mixture of regioisomers(1.70 grams, 81%).

Preparation 34:

1-(2-Fluoro-4-nitrophenyl)-1H-[1,2,4]-triazole

To a suspension of anhydrous potassium bicarbonate (8.30 grams, 60 mmol)in DMF (50 mL) was added 3,4-difluoronitrobenzene (5.0 grams, 31.4 mmol)followed by the addition of [1,2,4]-triazole (2.6 grams, 37.6 mmol) andheated to 80° C. for 1 hours. The reaction mixture was poured ontocrushed ice and the precipitate was filtered off. It was then washedwith water and dried under vacuum to yield the title compound as whitesolid (5.85 grams, 90%).

¹H NMR (CDCl₃): δ 8.85 (s, J=2.4 Hz, 1H), 8.32-8.11 (m, 4H); MS (m/e):209 (M++1), 195; IR (KBr, cm⁻⁴): 1533, 1510; 1346.

Preparation 35:

3-Fluoro-4-(1H-[1,2,4]-triazol-1-yl-phenylamine

To a mixture of nickel chloride hexahydrate (6.7 grams, 28.8 mmol) and1-(2-fluoro-4-nitrophenyl)-1H-[1,2,4]-triazole (3.0 grams, 14.4 mmol),obtained in preparation 34, in methanol (70 mL) was added sodiumborohydride (1.65 grams, 43.3 mmol) in portion and stirred for 0.5hours. The reaction mixture was then diluted with ethyl acetate (150 mL)and the organic layer was washed with water followed by brine and driedover sodium sulfate. Evaporation of volatiles yielded the title compoundas light brown solid (2.2 grams, 85%).

¹H NMR (CDCl₃): δ 8.48 (d, J=1.9 Hz, 1H), 8.11 (s, 1H), 7.54 (t, J=8.5Hz, 1H), 6.59 (s, 1H), 6.54 (d, J=2.9 Hz, 1H), 4.01 (bs, 2H); MS (m/e):179 (M⁺+1), 124; IR (KBr, cm⁻¹): 3376, 3225, 1630, 1527.

Preparation 36:

1-(4-Azido-2-fluorophenyl)-1H-[1,2,4]triazole

Sodium nitrite (1.55 grams, 22.5 mmol) was slowly added to an ice cooledsolution of 3-fluoro-4-(1H-[1,2,4]-triazol-1-yl)phenyl amine (2.0 grams,11.0 mmol), obtained in preparation 35, in 6N HCl (20 mL), and stirredfor 1 hours. A saturated solution of sodium azide (1.43 grams, 22.0mmol) and sodium acetate (18.50 grams, 220 mmol) in water (50 mL) wasadded slowly at the same temperature. The reaction mixture was dilutedwith ethyl acetate (500 mL). The organic layer was washed with waterfollowed by brine and dried over sodium sulfate. Evaporation ofvolatiles yielded the title compound as light brown solid (2.0 grams,87%).

¹H NMR (CDCl₃): δ 8.62 (d, J=2.9 Hz, 1H), 8.12 (s, 1H), 7.90 (t, J=8.5Hz, 1H), 7.05-6.85 (m, 2H); MS (m/e): 206 (M⁺+2), 205, 177, 176; IR(KBr, cm⁻¹): 2924, 2119, 1515, 1289.

Preparation 37:

[1-(4-Amino-3,5-difluoro-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester

To a solution of{1-[4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3,5-difluoro-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester (663 mg, 1.54 mmol), in methanol (3 mL) was addedethylene diamine (555 mg, 9.2 mmol) and stirred at room temperature for3 hours. Removal of methanol on rotavapor and purification of theresulting residue through a silica gel column (ethyl acetate/pet. ether,3:1) yielded the title compound as brown colour solid (402 mg, 88%)

¹H NMR(CDCl₃): δ 8.70 (bs, 1H), 8.11 & 7.97 (2 s, 1H, rotamers in aratio of 4:1), 7.28 (d, J=7.3 Hz, 2H), 4.86 & 4.58 (2 d, J=5.8, 2H,rotamers in a ratio of 4:1), 4.4 (s, 2H), 4.07 & 3.98 (2 s, 3H, rotamersin a ratio of 1:4); MS (m/e): 300(M⁺+1), 270, 181, 128; IR (KBr, cm⁻¹):3400, 3307, 3198, 2925, 1532, 1477.

Preparation 38:

1-(4-Azido-2,6-difluorophenyl)-1H-pyrrole

The title compound was prepared from 4-azido-2,6-difluoro-phenylamine,obtained in preparation 19, and 2,5-dimethoxy tetrahydrofuran, followingthe procedure reported in preparation 12.

¹H NMR (CDCl₃): δ 6.85 (s, 2H), 6.73 (d, J=8.6 Hz, 2H), 6.36 (s, 2H); MS(m/e): 221 (M⁺+1), 195; IR (KBr, cm⁻¹): 2117, 1640, 1589, 1527.

Preparation 39:

[1-(2-fluoro-4-nitro-phenyl)-1H-imidazol-4-yl]-methanol

3,4-Difluoronitrobenzene (2 grams, 12.5 mmol) and4-(hydroxymethyl)-imidazole hydrochloride (1.86 grams, 13.8 mmol) weretaken together in N,N-diisopropylethylamine (25 mL) and heated to 120°C. for 12 hours. Two layers were formed after the reaction mixture wasallowed to cool to room temperature. Upper layer was decanted and ethylacetate (500 mL) was added to the remaining portion. The ethyl acetatelayer was washed with water followed by brine and dried over sodiumsulfate. Evaporation of solvent yielded the tilte compound as brownsolid (2 grams, 67%).

¹H NMR (DMSO-d⁶): δ 8.43 (dd, J=2.2&11 Hz, 1H), 8.31-8.10 (m, 2H), 7.97(t, J=8.3 Hz, 1H), 7.54 (s, 1H), 5.09 (bs, 1H), 4.44 (d, J=4.3 Hz, 2H).

Preparation 40:

4-(tert-Butyl-dimethyl-silanyloxymethyl)-1-(2-fluoro-4-nitro-phenyl)-1H-imidazole

To an ice cooled solution of[1-(2-fluoro-4-nitrophenyl)-1H-imidazol-4-yl]-methanol (1.00 grams, 4.21mmol), obtained in preparation 39, and imidazole (574 mg, 8.42 mmol) inDMF (10 mL) was added tert-butyldimethylsilyl (TBDMS) chloride (953 mg,6.33 mmol). The reaction mixture was stirred at room temperature for 18hours. Evaporation of solvent under reduced pressure and purification ofthe resulting residue by column chromatography (pet ether/ethyl acetate,70:30) afforded-the title compound as a light brown solid (890 mg, 60%).

¹H NMR (DMSO-d₆): δ 8.34 (dd, J=10.9 Hz, 1H), 8.20-8.10 (m, 2H), 7.90(t, J=8.3 Hz, 1H), 7.48 (s, 1H), 4.50 (s, 2H), 0.80 (s, 9H), 0.09 (s,6H); MS (m/e): 352 (M⁺+1), 294; IR (KBr, cm⁻¹): 3436, 3126, 2931, 2859,1537.

Preparation 41:

4-(tert-Butyl-dimethyl-silanyloxymethyl)-1-(2-fluoro-4-amino-phenyl)-1H-imidazole

To a solution of4-(tert-butyl-dimethyl-silanyloxymethyl)-1-(2-fluoro-4-nitro-phenyl)-1H-imidazole(800 mg, 2.28 mmol), obtained in preparation 40, in methanol (30 mL) wasadded NiCl₂.6H₂O (1.00 grams, 4.55 mmol) followed by the addition ofsodium borohydride (259 mg, 6.83 mmol) and stirred at room temperaturefor 1 hours. The reaction mixture was then diluted with ethyl acetate(300 mL) and water (50 mL). The organic layer was separated, washed withbrine and dried over sodium sulfate. The solvent was evaporated to getthe compound as a brown thick material (585 mg, 80%).

¹H NMR (DMSO-d₆): δ 7.64 (s, 1H), 7.10-7.01 (m, 2H), 6.51-6.30 (m, 2H),5.61 (bs, 2H), 4.51 (s, 2H), 0.81 (s, 9H), 0.03 (s, 6H); MS (m/e): 322(M⁺+1), 264, 190; IR (KBr, cm⁻¹): 3344, 3213, 1637, 1530.

Preparation 42:

[1-(4-Azido-2-fluoro-phenyl)-1H-imidazol-4-yl]-methanol

Sodium nitrite (249 mg, 3.61 mmol) was slowly added to a solution of4-(tert-butyl-dimethyl-silanyloxymethyl)-1-(2-fluoro-4-amino-phenyl)-1H-imidazole(580 mg, 1.80 mmol), obtained in preparation 41, in 2N HCl (10 mL) at 0°C. and stirred for 1 hours. An aqueous solution containing NaN₃ (234 mg,3.61 mmol) and NaOAc (2.60 grams, 31.1 mmol) was added to the reactionmixture. The reaction mixture was diluted with EtOAc (300 mL), Theorganic phase was washed with water (2×100 mL) followed by brine anddried over sodium sulfate. Removal of volatiles and purification of theresulting residue by column chromatography (chloroform/methanol, 96:4)afforded the title compound as light brown solid (315 mg, 75%).

¹H NMR (CDCl₃): δ 7.78 (bs, 1H), 7.36 (t, J=8.2 Hz, 2H), 6.94 (d, J=9.6Hz, 2H), 4.69 (s, 2H), 3.00 (bs, 1H); MS (m/e): 234 (M⁺+1), 206; IR(KBr, cm⁻¹): 3215, 2923, 2122, 1521.

Preparation 43:

1-(4-Azido-2-fluoro-phenyl)-1H-imidazol-4-carbaldehyde

To a solution of [1-(4-azido-2-fluoro-phenyl)-1H-imidazol-4-yl]-methanol(500 mg, 2.14 mmol), obtained in preparation 42, in DCM (10 mL) wasadded Dess Martin Reagent (1.2 grams, 3.2 mmol) and stirred for 15hours. Reaction mixture was diluted with ethyl acetate and the resultingsolution was washed with water followed by brine and dried over sodiumsulfate. Removal of volatiles and column chromatographic purification ofthe resulting residue (silica gel, methanol/chloroform) produced thetitle compound as off white solid (400 mg, 80%).

IR (KBr, cm⁻¹): 3433, 2123. 1703, 1541, 1521.

¹H NMR (DMSO-d₆): δ 9.83 (s, 1H), 8.45 (s, 1H), 8.24 (s, 1H), 7.70 (t,J=8.5 Hz, 1H), 7.42 (d, J=11.5 Hz, 1H), 7.18 (d, J=8.6 Hz, 1H).

MS (m/e): 232 (M⁺+1).

Preparation 44:

1-(4-Azido-2-fluoro-phenyl)-1H-imidazol-4-carbaldehyde oxime

A mixture of 1-(4-azido-2-fluoro-phenyl)-1H-imidazol-4-carbaldehyde (400mg, 1.73 mmol), obtained in preparation 43, hydroxyl amine hydrochloride(179 mg, 2.59 mmol) and pyridine (205 mg, 2.59 mmol) in methanol (15 mL)was refluxed for 2 hours. The reaction mixture was diluted with ethylacetate and the resulting solution was washed with water followed bybrine and dried over sodium sulfate. Removal of volatiles and columnchromatographic purification of the resulting residue yielded the titlecompound (340 mg, 80%).

IR (KBr, cm⁻¹): 3067, 2855. 2117, 1520.

¹H NMR (DMSO-d₆): δ 11.66 (s, 1H), 8.11 (d, J=5.9 Hz, 2H), 7.60-7.70 (m,1H), 7.46 (s, 1H), 7.40 (d, J=1.9 Hz, 1H), 7.13 (d, J=8.6 Hz, 1H).

MS (m/e): 247 (M⁺+1), 229.

Preparation 45:

1-(4-Azido-2-fluoro-phenyl)-1H-imidazole-4-carbonitrile

To a solution of 1-(4-azido-2-fluoro-phenyl)-1H-imidazol-4-carbaldehydeoxime (340 mg, 1.38 mmol), obtained in preparation 44, in THF was added(methoxycarbonylsulfamoyl)triethylammonium hydroxide, inner salt(Burgess Reagent, 395 mg, 1.65 mmol) and refluxed for 3 hours.Evaporation of solvent and purification of the resulting residue bycolumn chromatographic purification produced the title compound (236 mg,75%).

IR (KBr, cm⁻¹): 2232, 2119, 1516.

¹H NMR (DMSO-d₆): δ 8.57 (s, 1H), 8.29 (s, 1H), 7.73 (t, J=8.6 Hz, 1H),7.43 (d, J=13.7 Hz, 1H), 7.19 (d, J=8.6 Hz, 1H).

MS (m/e): 229 (M⁺+1), 203.

Preparation 46:

[1-(2,6-Difluoro-4-nitro-phenyl)-1H-imidazol-4-yl]-methanol

This compound was prepared by following the procedure as described inprepration 39.

IR (KBr, cm⁻¹): 3139, 3043, 1529.

¹H NMR (CDCl₃): δ 8.05 (d, J=7.5 Hz, 2H), 7.83 (s, 1H), 7.26 (s, 1H),4.72 (s, 2H).

MS (m/e): 256 (M⁺+1), 236, 176.

Preparation 47:

4-(tert-Butyl-dimethyl-silanyloxymethyl)-1-(2,6-difluoro-4-nitro-phenyl)-1H-imidazole

This compound was prepared by following the procedure as described inprepration 40.

IR (KBr, cm−1): 2932, 2858, 1523, 1350.

¹H NMR (CDCl₃): δ 8.04 (d, J=7.3 Hz, 2H), 7.77 (s, 1H), 7.17 (s, 1H),4.78 (s, 2H), 0.9 (s, 9H), 0.13 (s, 6H).

MS (m/e): 370 (M⁺+1), 312, 238.

Preparation 48:

4-[4-(tert-Butyl-dimethyl-silanyloxymethyl)-imidazol-1-yl]-3,5-difluoro-phenylamine

This compound was prepared by following the procedure as described inprepration 41.

IR (Neat, cm¹): 3354, 2929, 1651, 1538.

¹H NMR (CDCl₃): δ 7.54 (s, 1H), 6.98 (s, 1H), 6.39 (d, J=9.8 Hz, 2H),4.78 (s, 3H), 0.95 (s, 9H), 0.13 (s, 6H).

MS (m/e): 340 (M⁺+1), 282, 208.

Preparation 49:

[1-(4-Azido-2,6-difluoro-phenyl)-1H-imidazol-4-yl]-methanol

This compound is prepared by following the procedure as described inprepration 42.

IR (KBr, cm⁻¹): 3156, 2112.

¹H NMR (CDCl₃): δ 7.66 (s, 1H), 7.09 (s, 1H), 6.78(d, J=8.5 Hz, 2H),4.69 (s, 2H).

MS (m/e): 252 (M++1), 226.

Preparation 50:

1-(4-Azido-2,6-difluoro-phenyl)-1H-imidazol-4-carbaldehyde

This compound was prepared by following the procedure as described inprepration 43.

IR (KBr, cm⁻¹): 2191, 2127, 1699.

¹H NMR (CDCl₃): δ 9.82 (s, 1H), 8.41 (s, 1H), 8.19 (s, 1H), 7.35(d,J=8.6 Hz, 2H).

MS (m/e): 250 (M⁺+1), 224.

Preparation 51:

1-(4-Azido-2,6-difluoro-phenyl)-1H-imidazol-4-carbaldehyde oxime

This compound was prepared by following the procedure as described inprepration 44.

IR (KBr, cm⁻¹): 3433, 3184, 3010, 2858, 2119, 1528.

¹H NMR (CDCl₃): δ 11.66 & 10.98 (2s in a ratio of 3:1, 1H), 8.05(d, J=12Hz, 2H), 7.40 (s, 1H), 7.30(d, J=8.9 Hz, 2H).

MS (m/e): 265 (M⁺+1), 247, 221.

Preparation 52:

1-(4-Azido-2,6-difluoro-phenyl)-1H-imidazole-4-carbonitrile

This compound was prepared by following the procedure as described inprepration 45.

IR (KBr, cm⁻¹): 3421, 2925, 2133, 1521.

¹H NMR (CDCl₃): δ 8.54 (s, 1H), 8.27 (s, 1H), 7.31 (d, J=8.9 Hz, 2H).

MS (m/e): 247 (M⁺+1), 218, 166, 126.

Preparation 53:

{1-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-fluoro-phenyl]-1H-[1,2,3]triazol-4-yl-methyl}-thiocarbamicacid O-methyl ester

To a DMF solution (2 mL) of2-(4-azido-2-fluoro-phenyl)-isoindole-1,3-dione (142 mg, 0.58 mmol),obtained in preparation 10, and diisopropylethyl amine (75 mg, 0.58mmol) was added prop-2-ynyl-thiocarbamic acid O-methyl ester (100 mg,0.78 mmol) followed by the addition of cuprous iodide (196 mg, 1.03mmol) in portion and stirred at room temperature for 0.5 hours.Saturated solution of ammonium chloride (5 mL) was added to the reactionmixture followed by the addition of two drops of ammonium hydroxidesolution. The reaction mixture was then diluted with ethyl acetate (50mL) and aqueous layer was separated. The organic phase was washed withwater followed by brine and dried over sodium sulfate. Evaporation ofvolatiles on rotavapor and purification of the resulting residue throughsilica gel column (ethyl acetate/pet ether, 1:1) yielded the titlecompound (124 mg, 60%).

¹H NMR (CDCl₃): δ 8.17 (s, 1H), 8.02-7.93 (m, 2H), 7.90-7.62 (m, 4H),7.55 (t, J=7.5 Hz, 1H), 6.92 (bs, 1H), 4.93 & 4.72 (2 d, J=5.9 Hz, 2H,rotamers in a ratio of 4:1), 4.13 & 4.01 (2s, 3H, rotamers in a ratio of1:4); MS (m/e): 412 (M⁺+1), 380, 323, 257; IR (KBr, cm⁻¹): 1731, 1528,1384.

Preparation 54:

[1-(4-Amino-3-fluoro-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester

To a solution of{1-[4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-fluoro-phenyl]-1H-[1,2,3]triazol-4-yl-methyl}-thiocarbamicacid O-methyl ester (75 mg, 0.182 mmol), obtained in preparation 53, inmethanol (3 mL) was added ethylene diamine (60 mg, 1.08 mmol) andstirred at room temperature for 3 hours. Removal of methanol onrotavapor and purification of the resulting residue through a silica gelcolumn (ethyl acetate/pet ether, 3:1) yielded the title compound asbrown colour solid (46 mg, 91%).

¹H NMR (CDCl₃): δ 7.91 & 7.69 (2s, rotamers in a ratio of 4:1, 1H), 7.33(d, J=11.3 Hz, 1H), 7.17 (bs, 1H), 6.99 (bs, 1H), 6.79 (t, J=8.9 Hz,1H), 4.82 & 4.57 (2 d, J=5.7 Hz, 2H, rotamers in a ratio of 4:1), 4.04 &3.92 (2s, 3H, rotamers in a ratio of 1:4); MS (m/e): 282 (M⁺+1), 250.

Preparation 55:

{1-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3,5-difluoro-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester

To a DMF solution (2 mL) of2-(4-azido-2,6-difluorophenyl)-isoindole-1,3-dione (1 g, 3 mmol),obtained in preparation 18, and diisopropylethyl amine (388.5 mg, 3mmol) was added prop-2-ynyl-thiocarbamic acid O-methyl ester (580 mg,4.5 mmol) followed by the addition of cuprous iodide (1.14 grams, 6mmol) in portion and stirred at room temperature for 0.5 hours.Saturated solution of ammonium chloride (5 mL) was added to the reactionmixture followed by the addition of few drops of ammonium hydroxidesolution. The solution was then diluted with ethyl acetate (500 mL) andaqueous layer was separated. The organic layer was washed with waterfollowed by brine and dried over sodium sulfate. Evaporation ofvolatiles on rotavapor and purification of the resulting residue throughsilica gel column (ethyl acetate/pet ether: 1:4) yielded the titlecompound (663 mg, 76%).

¹H NMR (CDCl₃): δ 8.18 (s, 1H), 8.05-7.96 (m, 2H), 7.91-7.77 (m, 2H),7.58 (d J=7.8 Hz, 2H), 6.88 (bs, 1H), 4.94 & 4.72 (2 d, J=5.8 Hz, 2H,rotamers in a ratio of 4:1), 4.13 & 4.01 (2 s, 3H, rotamers in a ratioof 1:4); MS (m/e): 430 (M⁺+1), 398, 311, 275; IR (KBr, cm⁻¹): 3438,2924, 2854, 1739.

EXAMPLE 1[1-(4-Pyrrol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester

To a solution of[1-(4-amino-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamic acidO-methyl ester (0.10 grams, 0.4 mmol), obtained in preparation 7, inglacial acetic acid (10 mL) was added 2,5-dimethoxy tetrahydrofuran(0.06 grams, 0.42 mmol) and heated to 80° C. for 0.5 hours. The reactionmixture was then diluted with ethyl acetate (50 mL) and the organicphase was washed with water followed by brine and dried over sodiumsulfate. Evaporation of volatiles on rotavapor and purification of theresulting residue through a silica gel column (ethyl acetate/chloroform,1:4) yielded the title compound as white solid (70 mg, 60%). mp 150° C.

¹HNMR (CDCl₃): δ 8.13 (s, 1H), 7.80 (d, J=8.6 Hz, 2H), 7.55 (d, J=8.6Hz, 2H), 7.12 (m, 1H), 7.01 (bs, 1H, D₂O exchangeable), 6.44 (m, 1H),4.91 & 4.78 (2 d, J=5.9 Hz, 2H, rotamers in a ratio of 4:1), 4.15 & 4.09(2 s, 3H, rotamers in a ratio of 1:4); MS (m/e): 314 (M³⁰ +1).

EXAMPLE 2{1-[4-(3-Formyl-pyrrol-1-yl)-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O methyl ester

To a solution of[1-(4-aminophenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamic acidO-methyl ester (0.10 grams, 0.4 mmol), obtained in preparation 7, inglacial acetic acid (10 mL) was added 2,5-dimethoxytetrahydrofuran-3-carboxaldehyde (0.06 g, 0.42 mmol) and heated to 80°C. for 0.5 hours. The reaction mixture was diluted with ethyl acetate(20 mL) and the organic layer was washed with water followed by brineand dried over sodium sulfate. Evaporation of volatiles on rotavapor andpurification of the resulting residue through a silica gel column (ethylacetate/chloroform, 1:4) yielded the title compound as white solid (70mg, 53%). mp 160-162° C.

¹HNMR (CDCl₃): δ 9.91 (s, 1H), 9.23 (bs, 1H, D₂O exchangeable), 8.40 (s,1H), 7.95 (d, J=8.8 Hz, 2H), 7.72 (d, J=8.8 Hz, 2H), 7.30 (m, 1H), 6.84(s, 1H), 4.91 & 4.65 (2 d, J=5.9 Hz, 2H, rotamers in a ratio of 4:1),4.03 & 3.91 (2 s, 3H, rotamers in a ratio of 1:4); MS (m/e): 342 (M⁺+1),310.

EXAMPLE 3{1-[4-(3-Hydroxymethyl-pyrrol-1-yl)-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester

Sodium borohydride (11 mg, 0.28 mmol) was added to a solution of{1-[4-(3-formyl-pyrrol-1-yl)-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester (30 mg, 0.09 mmol), obtained in example 2, inmethanol (4 mL) at 0° C. and stirred for 3 hours. Methanol was removedon a rotavapor and the crude residue was purified through a silica gelcolumn (ethyl acetate/pet ether, 1:1) to yield the title compound aslight yellow solid (28 mg, 93%).

¹HNMR (CDCl₃+DMSO-d₆): δ 9.46 (bs, 1H), 8.49 (s, 1H), 8.02 (s, 1H), 7.92(d, J=8.3 Hz, 2H), 7.64 (d, J=8.3 Hz, 2H), 7.23 (s, 1H), 6.34 (s, 1H),4.82 & 4.70 (2 d, J=5.4 Hz, 2H, rotamers in a ratio of 4:1), 4.58-4.45(m, 2H), 4.03 & 3.96 (2 s, 3H, rotamers in a ratio of 1:4); MS (m/e):344 (M⁺+1), 312, 294; IR (KBr, cm⁻¹): 3356, 2924, 1676.

EXAMPLE 4[1-(3-Fluoro-4-pyrrol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester

To a DMF solution (2 mL) of 1-(4-azido-2-fluorophenyl)-1H-pyrrole (82mg, 0.41 mmol), obtained in preparation 12, and diisopropylethyl amine(53 mg, 0.41 mmol) was added prop-2-ynyl-thiocarbamic acid O-methylester (82 mg, 0.61 mmol) followed by the addition of cuprous iodide (154mg, 0.81 mmol) in portion and stirred at room temperature for 0.5 hours.Saturated solution of ammonium chloride (5 mL) was added to the reactionmixture followed by the addition of two drops of ammonium hydroxidesolution. The reaction mixture was then diluted with ethyl acetate (50mL) and aqueous layer was separated. The organic layer was washed withwater followed by brine and dried over sodium sulfate. Evaporation ofvolatiles on rotavapor and purification of the resulting residue throughsilica gel column (ethyl acetate/pet ether, 1:2) yielded the titlecompound as light brown solid (34 mg, 25%).

¹H NMR (CDCl₃): δ 8.14 (s, 1H), 7.68 (d, J=12.2 Hz, 1H), 7.50 (bs, 2H),7.08 (s, 2H), 6.94 (bs, 1H), 6.40 (s, 2H), 4.92 & 4.65 (2 d, J=5.9 Hz,2H, rotamers in a ratio of 4:1), 4.12 & 4.00 (2 s, 3H, rotamers in aratio of 1:4); MS (m/e): 332 (M⁺+1), 300, 213; IR (KBr, cm⁻): 3427,2925, 2854, 1534.

EXAMPLE 5{1-[4-(3-Cyano-pyrrol-1-yl)-3-flouro-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester

To a DMF solution (2 mL) of1-(4-azido-2-fluoro-phenyl)-1H-pyrrole-3-carbonitrile (60 mg, 0.26mmol), obtained in preparation 15, was added prop-2-ynyl-thiocarbamicacid O-methyl ester (44 mg, 0.34 mmol) followed by the addition ofcuprous iodide (100 mg, 0.53 mmol) in portion and stirred at roomtemperature for 0.5 hours. Saturated solution of ammonium chloride (5mL) was added to the reaction mixture followed by the addition of fewdrops of ammonium hydroxide solution. The reaction mixture was thendiluted with ethyl acetate (200 mL) and aqueous layer was separated. Theorganic phase was washed with water followed by brine and dried oversodium sulfate. Evaporation of volatiles on rotavapor and purificationof the resulting residue through silica gel column (ethyl acetate/petether: 1:1) yielded the title compound (56 mg, 61%).

¹H NMR (CDCl₃): δ 8.19 & 7.96 (2 s, 1H, rotamers in a ratio of 4:1 ),7.78 (d, J=11.2 Hz, 1H), 7.85-7.52 (m, 4H),7.03 (s, 1H), 6.92 (bs, 1H),6.66 (s, 1H), 4.93 & 4.7 J=5.8 Hz, 2H, rotamers in a ratio of 4:1), 4.13& 4.01 (2 s, 3H, rotamers in a ratio of 1:4); MS (m/e):357 (M⁺+1), 325,238; R (KBr, cm⁻¹): 3346, 2234, 1537.

EXAMPLE 6{1-[3-Fluoro-4-(3-formyl-pyrrol-1-yl)-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester

To a solution of[1-(4-amino-3-fluoro-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester (123 mg, 0.43 mmol), obtained in preparation 54, inglacial acetic acid (4 mL) was added 2,5-dimethoxytetrahydrofuran-3-carboxaldehyde (64 mg, 0.48 mmol) and heated to 114°C. for 3 hours. The reaction mixture was diluted with water (20 mL) andneutralized with saturated solution of sodium bicarbonate. The aqueouslayer was then extracted with ethyl acetate (50 mL×2) and the combinedextracts were washed with water followed by brine. After drying oversodium sulfate, ethyl acetate was removed on rotavapor and the resultingresidue was purified through a silica gel column (ethyl acetate/petether: 2:1) to yield the title compound as light brown solid (79 mg,50%).

¹HNMR (CDCl₃): δ 9.87 (s, 1H), 8.17 & 7.95 (2 s, 1H, rotamers in a ratioof 4:1), 7.76 (d, J=11.2 Hz, 1H), 7.65-7.51 (m, 3H), 7.06 (s, 1H), 6.92(bs, 1H), 4.92 & 4.67 2 d, J=5.9 Hz, 2H, rotamers in a ratio of 4:1),4.11 & 3.99 (2 s, 3H, rotamers in a ratio of 1:4); MS (m/e): 360 (M⁺+1),328, 298; IR (KBr, cm⁻¹): 3356, 2924, 1676.

EXAMPLE 7[1-(3,5-difluoro-4-pyrrol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester

To a solution of[1-(4-amino-3,5-difluoro-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester (180 mg, 0.6 mmol), obtained in preparation 37, inglacial acetic acid (3 mL) was added 2,5-dimethoxy tetrahydrofuran(79.23 mg, 0.6 mmol) and heated to 100° C. for 4 hours. The reactionmixture was diluted with water (20 mL) and neutralized with saturatedsolution of sodium bicarbonate. The aqueous layer was then extractedwith ethyl acetate (50 mL×2) and the combined extracts were washed withwater followed by brine. After drying over sodium sulfate, ethyl acetatewas removed on rotavapor and the resulting residue was purified bypassing through a silica gel column (ethyl acetate/pet ether: 1:1) toyield the title compound as light brown solid (169 mg, 81%).

¹HNMR (CDCl₃): δ 8.16 & 7.96 (2 s, 1H, rotamers in a ratio of 4:1), 7.52(d, J=8.3 Hz, 2H), 6.95 (s, 3H), 6.41 (s, 2H), 4.93 & 4.78 (2 d, J=5.9,2H, rotamers in a ratio of 4:1), 4.13 & 4.01 (2 s, 3H, rotamers in aratio of 1:4); MS (m/e): 350 (M⁺+1), 321, 306, 231; IR (KBr, cm⁻¹):3315, 2926, 1538, 1035.

EXAMPLE 8{1-[4-(3-Cyano-pyrrol-1-yl)-3,5-difluoro-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester

To a DMF solution (2 mL) of1-(4-azido-2,6-difluoro-phenyl)-1H-pyrrole-3-carbonitrile (166 mg, 0.68mmol), obtained in preparation 22, and diisopropylethyl amine (88 mg,0.88 mmol) was added prop-2-ynyl-thiocarbamic acid O-methyl ester (131mg, 1.02 mmol) followed by the addition of cuprous iodide (257 mg, 1.36mmol) in portion and stirred at room temperature for 4 hours. Saturatedsolution of ammonium chloride (5 mL) was added to the reaction mixturefollowed by the addition of few drops of ammonium hydroxide solution.The reaction mixture was then diluted with ethyl acetate (200 mL) andaqueous layer was separated. The organic phase was washed with waterfollowed by brine and dried over sodium sulfate. Evaporation ofvolatiles on rotavapor and purification of the resulting residue throughsilica gel column (ethyl acetate/pet ether: 1:2) yielded the titlecompound; (56 mg, 22%).

¹H NMR (CDCl₃): δ 8.17 & 7.91(2 s, 1H, rotamers in a ratio of 4:1), 7.58(d, J=8.3 Hz, 2H), 7.39 (s, 1H), 6.90 (bs, 2H), 6.64 (s, 1H), 4.91 &4.66 (2 d, J=5.8 Hz, 2H, rotamers in a ratio of 4:1), 4.10 & 3.98 (2 s,3H, rotamers in a ratio of 1:4); MS (m/e):375 (M⁺+1), 343, 256, 181; IR(KBr, cm⁻¹): 3239, 2924, 2226, 1543, 1044.

EXAMPLE 9[1-(3,5-Difluoro-4-imidazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester

To a DMF solution (5 mL) of 1-(4-azido-2,6-difluorophenyl)-1H-imidazole(500 mg, 2.26 mmol), obtained in preparation 25, and-diisopropylethylamine (291 mg, 2.26 mmol) was added prop-2-ynyl-thiocarbamic acidO-methyl ester (321 mg, 2.48 mmol) followed by the addition of cuprousiodide (859 mg, 4.52 mmol) in portion and stirred at room temperaturefor 0.5 hours. Saturated solution of ammonium chloride (20 mL) was addedto the reaction mixture followed by the addition of few drops ofammonium hydroxide solution. The blue colour solution was diluted withethyl acetate (100 mL) and aqueous layer was separated. The organiclayer was washed with water followed by brine and dried over sodiumsulfate. Evaporation of volatiles on rotavapor and purification of theresulting residue through silica gel column yielded the pink colorcompound (220 mg, 28%). mp 180° C.

¹H NMR (CDCl₃): δ 9.71 (s, 1H), 8.89 & 8.85 (2 s, 1H, rotamers in 4:1ratio), 8.13 (d, J=9.5 Hz, 2H), 8.02 (s, 1H), 7.53 (s, 1H), 7.12 (s,1H), 4.77 & 4.48 (2 d, J=5.4 Hz, 2H, rotamers in 4:1 ratio), 3.96 & 3.90(2 s, 3H, rotamers 1:4 ratio); MS (m/e): 351 (M⁺+1), 319; IR (KBr,cm⁻¹): 3443, 1535.

EXAMPLE 10[1-(3-Fluoro-4-imidazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thiocarbamicacid O-methyl ester

To a DMF solution (5 mL) of 1-(4-azido-2-fluorophenyl)-1H-imidazole (500mg, 2.46 mmol), obtained in preparation 28, and diisopropylethyl amine(317 mg, 2.46 mmol) was added prop-2-ynyl-thiocarbamic acid O-methylester (349 mg, 2.7 mmol) followed by the slow addition of cuprous iodide(934 mg, 4.92 mmol) and stirred at room temperature for 0.5 hours.Saturated solution of ammonium chloride (20 mL) was added to thereaction mixture followed by the addition of few drops of ammoniumhydroxide solution. The blue colour solution was diluted with ethylacetate (100 mL) and aqueous layer was separated. The organic layer waswashed with water followed by brine and dried over sodium sulfate.Evaporation of volatiles on rotavapor and purification of the residue bysilica gel column chromatography yielded the pink color compound (245mg, 30%). mp 165-167° C.

¹H NMR (CDCl₃+DMSO-d₆): δ 9.01 (bs, 1H), 8.40 & 8.28 (2 s, 1H, rotamersin 4:1 ratio), 7.99 (s, 1H), 7.90 (dd, J=2.1 & 11.3 Hz, 1H), 7.80-7.60(m, 2H), 7.39 (s, 1H), 7.25 (s, 1H), 4.87 & 4.62 (2 d, J=5.6 Hz, 2H,rotamers in 4:1 ratio), 4.06 & 3.99 (2 s, 3H, rotamers in 1:4 ratio); MS(m/e): 332 (M⁺+1), 301, 246, 214; IR (KBr, cm⁻¹): 3431, 1535.

EXAMPLE 114-Azidomethyl-1-(3-fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazole

Sodium azide (0.98 grams, 15 mmol) was added to a mixture ofmethanesulfonic acid[1-(3-fluoro-4-pyrazol-1-ylphenyl)-1H-[1,2,3]triazol-4-yl]-methyl ester& methanesulfonic acid[1-(3-fluoro-4-pyrazol-1-ylphenyl)-1H-[1,2,3]triazol-5-yl]-methyl ester(1.70 grams, 5 mmol), obtained in preparation 33, in DMF (15 mL) andheated to 90° C. for 1 h. The reaction mixture was diluted with water(50 mL) and extracted with ethyl acetate (50 mL×3). The combinedextracts were washed with water followed by brine and dried over sodiumsulfate. Evaporation of volatiles and purification of the resultingresidue by column chromatography yielded the required regioisomer aspale yellow solid (800 mg, 55%).

¹H NMR (DMSO-d₆): δ 8.99 (s, 1H), 8.32 (s, 1H), 8.24 (dd, J=2.3 & 20.2Hz, 1H), 8.11-7.93 (m, 2H), 7.86 (s, 1H), 6.65 (s, 1H), 4.61 (s, 2H); MS(m/e): 285 M⁺+1); IR (KBr, cm⁻¹): 3426, 2083, 1533.

EXAMPLE 12C-[1-(3-Fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl]methylamine

A mixture of4-azidomethyl-1-(3-fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazole (800mg, 3.10 mmol), obtained in example 11, and triphenylphosphine (894 mg,3.40 mmol) in THF (10 mL) was stirred at room temperature for 3 hours.It was then warmed to 40° C. after the addition of 4-5 drops of waterand allowed to stir at the same temperature for 16 hours. The reactionmixture was diluted with water and extracted with ethyl acetate (50mL×2). Combined ethyl acetate extracts were washed with water followedby brine and dried over sodium sulfate. Evaporation of volatiles andpurification of the resulting residue by column chromatography withsilica gel (60-120 mesh) yielded the title compound as pale yellow solid(580 mg, 80%).

¹H NMR (DMSO-d₆): δ 8.72 (s, 1H), 8.30 (s, 1H), 8.20-7.86 (m, 4H), 6.67(s, 1H), 3.81 (s, 2H), 2.85 (bs, 2H); MS (m/e): 259 (M⁺+1); IR (KBr,cm⁻¹): 3382, 3156, 3114, 2923, 1536.

EXAMPLE 13[1-(3-Fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl-methyl]-thiocarbamicacid O-methyl ester

To a mixture ofC-[1-(3-fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl]-methylamine(300 mg, 1.16 mmol), obtained in example 12, in CHCl₃ (40 mL) andsaturated sodium bicarbonate solution (5 mL), was added thiophosgene(133 mg, 1.16 mmol) and stirred at room temperature for 0.5 hours. Thereaction mixture was diluted with ethyl acetate (50 mL) and the organiclayer was washed with water followed by brine and dried over sodiumsulfate. Evaporation of volatiles left a residue, which was refluxedwith methanol (30 mL) for 16 hours. Removal of methanol on rotavapor andpurification of the resulting residue through a silica gel column(60-120 mesh) yielded the title compound as white solid (180 mg, 46%).

¹H NMR (CDCl₃): δ 8.22-7.95 (m, 3H), 7.81-7.52 (m, 3H), 6.97 (bs, 1H),6.53 (s, 1H), 4.92 & 4.69 (2d, J=4.8 Hz, rotamers in the ratio of 1:4,2H)), 4.15 & 4.03 (2s, rotamers in the ration of 1:4, 3H); MS (m/e):333, 301, 214 (M⁺+1); IR (KBr, cm⁻¹): 3187, 3023, 2933, 1535.

EXAMPLE 14N-[1-(3-Fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl-methyl]acetamide

A solution of4-azidomethyl-1-[3-fluoro-4-pyrazol-1-yl-phenyl]-1H-[1,2,3]triazole (500mg), obtained in example 11, in thiolacetic acid (1 mL) was stirred for12 hours at room temperature. The reaction mixture was then absorbed onsilica gel and purified by column chromatography (over silica gel) toyield the title compound as off white solid (350 mg, 66%).

¹H NMR (DMSO-d₆): δ 8.20-8.09 (m, 3H), 7.81-7.78 (m, 2H), 7.62 (d, J=8.7Hz, 1H), 6.53 (s, 1H), 6.28 (bs, 1H), 2.03 (s, 3H); MS (m/e): 301(M⁺+1); IR (KBr, cm⁻¹): 3303, 3125, 3080, 1659 and 1537.

EXAMPLE 15N-[1-(3-Fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl-methyl]-thioacetamide

To a solution ofN-[1-(3-fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl-methyl]-acetamide(150 mg, 0.50 mmol), obtained in example 14, in 1,4-dioxane (5 mL) wasadded Lawessen's reagent (242 mg, 0.60 mmol) and refluxed for 12 hours.The reaction mixture was diluted with ethyl acetate (50 mL) and theorganic portion was washed with water followed by brine and dried oversodium sulfate. Evaporation of volatiles left a residue, which waspurified by column chromatography (over silica gel) to yield the titlecompound as off white solid (100 mg, 63%).

¹H NMR (CDCl₃): δ 8.42 (bs, 1H), 8.30-8.11 (m, 3H), 7.82-7.55 (m, 3H),6.57 (s, 1H), 5.05 (d, J=5.6 Hz, 2H), 2.61(s, 3H); MS (m/e): 317 (M⁺+1);IR (KBr, cm⁻¹): 3220, 3019, 1536.

EXAMPLE 161-Ethyl-3-[1-(3-fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl-methyl]-thiourea

To a solution ofC-[1-(3-fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl]-methylamine(200 mg, 0.77 mmol), obtained in example 12, in dichloromethane (10 mL)was added triethylamine (172 mg, 1.70 mmol) followed by the addition ofethylisothiocyanate (135 mg, 1.55 mmol) at 0° C. and stirred at roomtemperature for 18 hours. The reaction mixture was diluted with ethylacetate (100 mL) and washed with water followed by brine and dried oversodium sulfate. Evaporation of volatiles on rotavapor and purificationof the resulting residue by column chromatography (over silica gel)yielded the title compound as pale yellow solid (110 mg, 41%).

¹H NMR (DMSO-d₆): δ 8.78 (s, 1H), 8.32-7.81 (m, 6H), 7.57 (bs, 1H), 6.61(s, 1H), 4.78 (d, J=4.9 Hz, 2H), 3.38 (bs, 2H, after D₂O exchange), 1.0(t, J=7.1 Hz, 3H); MS (m/e): 346 (M⁺+1), 317, 301, 259, 214; IR (KBr,cm⁻¹): 3330, 1532, 1396, 1043.

EXAMPLE 171-[3-Fluoro-4-pyrazol-1-yl-phenyl]-1H-[1,2,3]triazol-4-yl-methylamino-hydrazinomethanethione

To a solution ofC-[1-(3-fluoro-4-pyrazol-1-ylphenyl)-1H-[1,2,3]triazol-4-yl]-methylamine(250 mg, 0.97 mmol), obtained in example 12, in DMF (2 mL) was added4-(4-methylphenyl)-3-thiosemicarbazide (193 mg, 1.06 mmol) and heated to90° C. for 12 hours. The reaction mixture was then diluted with ethylacetate (150 mL) and washed with water followed by brine and dried oversodium sulfate. Evaporation of volatiles on rotavapor and purificationof the resulting residue by column chromatography (silica gel) yieldedthe title compound as off white powder (105 mg, 32%).

¹H NMR (DMSO-d₆): δ 8.82 (s, 1H), 8.65 (bs, 1H), 8.31 (s, 1H), 8.19-7.88(m, 4H), 7.80 (s, 1H), 6.62 (s, 1H), 4.45 (d, J=5.6 Hz, 2H); MS (m/e):287 (M⁺−45), 258, 229, 214, 202; IR (KBr, cm⁻¹): 3438, 3257, 1648, 1532.

EXAMPLE 18N-[1-(3-Fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl-methyl]-methane-sulfonamide

To a solution ofC-[1-(3-fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl]-methylamine(200 mg, 0.77 mmol), obtained in example 12, in dichloromethane (10 mL)was added triethylamine (156 mg, 1.55 mmol) followed by the addition ofmethanesulfonyl chloride (97 mg, 0.85 mmol) at 0° C. and stirred at thesame temperature for 1 h. The reaction mixture was diluted with ethylacetate (100 mL) and washed with water followed by brine and dried oversodium sulfate. Evaporation of volatiles under vacuum yielded the titlecompound as off white powder (180 mg, 69%).

¹H NMR (CDCl₃+DMSO-d₆): δ 8.51 (s, 1H), 8.15-7.70 (m, 5H), 7.63 (bs,1H), 6.59 (s, 1H), 4.45 (s, 2H), 3.01 (s, 3H); MS (m/e): 337(M⁺+1); IR(KBr, cm⁻¹): 3446, 3237, 1536, 1308.

EXAMPLE 19[1-(3-Fluoro-4-pyrazol-1-yl-phenyl]-1H-[1,2,3]triazol-4-yl]-methylcarbamic acid O-methyl ester

To a solution ofC-[1-(3-fluoro-4-pyrazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl]-methylamine(200 mg, 0.78 mmol), obtained in example 12, in dichloromethane (10 mL)was added N-ethyldiisopropylamine (219 mg, 1.7 mmol) followed by theaddition of methyl chloroformate (87 mg, 0.92 mmol) at 0° C. and stirredat the same temperature for 2 h. The reaction mixture was then dilutedwith ethyl acetate (150 mL) and washed with water followed by brine anddried over sodium sulfate. Removal of volatiles under reduced pressureand purification of the resulting residue by column chromatography (oversilica gel) yielded the title compound as white powder (150 mg, 61%).

¹H NMR (DMSO-d₆): δ 8.76 (s, 1H), 8.31 (s, 1H), 8.10 (d, J=12.6 Hz, 1H),8.01-8.10 (m, 2H), 7.91 (s, 1H), 6.59 (s,1H), 4.30 (d, J=5.8 Hz, 2H),3.57 (s, 3H); MS (m/e): 317 (M⁺+1); IR (KBr, cm⁻¹): 3366, 3128, 2926,1724, 1536.

EXAMPLE 20[1-(3-Fluoro-4-[1,2,4]triazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-yl-methyl]-thiocarbamicacid O-methyl ester

To a DMF solution (5 mL) of1-(4-azido-2-fluorophenyl)-1H-[1,2,4]triazole (250 mg, 1.23 mmol),obtained in preparation 36, and diisopropylethyl amine (155 mg, 1.2mmol) was added prop-2-ylnyl-thiocarbamic acid O-methyl ester (189 mg,1.47 mmol) followed by the addition of cuprous iodide (228 mg, 1.2 mmol)in portion and stirred at room temperature for 0.5 hours. Saturatedsolution of ammonium chloride (10 mL) was added to the reaction mixturefollowed by the addition of few drops of ammonium hydroxide solution.The blue colour solution was diluted with ethyl acetate (100 mL) andaqueous layer was separated. The organic layer was washed with waterfollowed by brine and dried over sodium sulfate. Evaporation ofvolatiles on rotavapor and purification of the resulting residue throughsilica gel column yielded the white color compound (220 mg, 32%). Mp179° C.

¹H NMR (CDCl₃): δ 9.72 (bs, 1H), 9.12 & 8.83 (2 s, 1H, rotamers in aratio of 4:1), 8.87 (s, 1H), 8.87 (s, 1H), 8.38-8.18 (m, 3H), 8.03 (s,1H), 4.77 & 4.45 (2 d, 2H, J=5.4 Hz, rotamers in a ratio of 1:4), 3.97 &3.91 (2 s, 3H); MS (m/e): 334 (M⁺+1), 305, 290, 215; IR (KBr, cm⁻¹):3447, 3184, 2925, 1530, 1215, 771.

EXAMPLE 21N-[1-(3,5-Difluoro-4pyrrol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-acetamide

To a DMF solution (3 mL) of 1-(4-azido-2,6-difluorophenyl)-1H-pyrrole(350 mg, 1.59 mmol), obtained in preparation 38, was added propargylamine N-acetamide (232 mg, 2.38 mmol) followed by the addition ofN,N-diisopropylethylamine (205 mg, 1.59 mmol). Cuprous iodide (604 mg,3.18 mmol) was added to the reaction mixture in portion and stirred atroom temperature for 0.5 hours. A saturated solution of ammoniumchloride (50 mL) was added followed by few drops of ammonium hydroxideand then the reaction mixture was extracted with ethylacetate (75 mL×2).Combined organic phase was washed with brine and dried over sodiumsulfate. Removal of volatiles and purification of the resulting residuethrough silica gel column (pet. ether/ethylacetate, 1:1) yielded 100 mg(20%) of the title compound.

¹H NMR (CDCl₃): δ 8.05 (s, 1H), 7.52 (d, J=8.3 Hz, 2H), 6.95 (s, 2H),6.41 (s, 2H), 6.31 (bs, 1H), 4.58 (d, J=5.6 Hz, 2 H), 2.03 (s, 3H); MS(m/e): 318 (M⁺+1), 289; IR (KBr, cm⁻¹): 3263, 2925, 1636, 1537.

EXAMPLE 22N-[1-(3-Fluoro-4-pyrrol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-acetamide

To an ice cooled DMF solution (3 mL) of1-(4-azido-2-fluorophenyl)-1H-pyrrole (300 mg, 1.49 mmol), obtained inpreparation 12, was added propargyl amine N-acetamide (173 mg, 1.78mmol) followed by the addition of N,N-diisopropylethylamine (192 mg,1.49 mmol). Cuprous iodide (566 mg, 2.98 mmol) was added to the reactionmixture in portion and stirred at the same temperature for 15 min., thenat room temperature for 2 hours. A saturated solution of ammoniumchloride, (50 mL) was added followed by few drops of ammonium hydroxideand then the reaction mixture was extracted with ethylacetate (75 mL×2).Combined organic phase was washed with brine and dried over sodiumsulfate. Removal of volatiles and purification of the resulting residuethrough silica gel column (pet. ether/ethylacetate, 1:2) yielded 250 mg(56%) of the title compound. Mp. 210-215° C.

¹H NMR (CDCl₃): δ 8.03 (s, 1H), 7.74-7.54 (m, 3H), 7.09 (d, J=2.1 Hz,2H), 6.40 (s, 2H), 6.25 (bs, 1H), 4.59 (d, J=5.9 Hz, 2H), 2.04 (s, 3H);MS (m/e): 300 (M⁺+1), 186; IR (KBr, cm⁻¹): 3303, 2925, 1659, 1536.

EXAMPLE 23N-[1-(3-Fluoro-4-imidazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-acetamide

The title compound was prepared from1-(4-azido-2-fluorophenyl)-1H-imidazole, obtained in preparation 28, andpropargyl amine N-acetamide following the procedure reported in example22. Mp. 198-199° C.

¹H NMR (CDCl₃+DMSO-d₆): δ 8.40 (s, 1H), 8.18 (bs, 1H), 8.01-7.50 (m,4H), 7.41 (s, 1H), 7.20 (s, 1H), 4.50 (d, J=5.4 Hz, 2 H), 1.98 (s, 3H);MS (m/e): 301 (M⁺+1), 273; IR (KBr, cm⁻¹): 3230, 3045, 1666, 1533.

EXAMPLE 24N-[1-(3-Fluoro-4-imidazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thioacetamide

A mixture of Lawesson's reagent (94 mg, 0.23 mmol) andN-[1-(3-fluoro-4-imidazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-acetamide(100 mg, 0.33 mmol), obtained in example 23, in dry dioxane (5 mL) washeated to 60° C. for 2 hours. The reaction mixture was then diluted withethyl acetate (100 mL) and washed with water followed by brine and driedover sodium sulfate. Removal of volatiles and purification of theresulting residue by column chromatography (chloroform/methanol, 96:4)yielded the title compound as cream color powder (50 mg, 48%). Mp. 185°C.

¹H NMR (CDCl₃+DMSO-d₆): δ 10.35 (bs, 1H), 8.67 (s, 1H), 8.01-7.65 (m,4H), 7.43 (s, 1H), 7.12 (s, 1H), 4.89 (d, J=4.9 Hz, 2 H), 2.48 (s, 3H);MS (m/e): 317 (M⁺+1), 289, 248, 214; IR (KBr, cm⁻¹): 3238, 2922, 1531.

EXAMPLE 25N-[1-(3-Fluoro-4-[1,2,4]triazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-acetamide

To a DMF solution (5 mL) of1-(4-azido-2-fluorophenyl)-1H-[1,2,4]triazole, obtained in preparation36, and N,N-diisopropylethyl amine (157 mg, 1.2 mmol) was addedpropargyl N-acetamide (142 mg, 1.46 mmol) followed by the addition ofcuprous iodide (228 mg, 1.2 mmol) in portion and stirred at roomtemperature for 0.5 hours. A saturated solution of ammonium chloride (10mL) was added to the reaction mixture followed by the addition of fewdrops of ammonium hydroxide. The reaction mixture was then diluted withethyl acetate (100 mL) and the aqueous layer was separated. The organicphase was washed with water followed by brine and dried over sodiumsulfate. Evaporation of volatiles and purification of the resultingresidue through a silica gel column yielded the title compound as whitepowder (105 mg, 28%). Mp. 223° C.

¹H NMR (CDCl₃): δ 9.12 (s, 1H), 8.79 (s, 1H), 8.47 (bs, 1H), 8.24 (d,J=12.7 Hz, 1H), 8.03 (bs, 2H), 4.40 (d, J=5.3 Hz, 2 H), 1.88 (s, 3H); MS(m/e): 302 (M⁺+1), 273 181; IR (KBr, cm³¹ ¹): 3286, 2925, 1670, 1259.

EXAMPLE 26N-[1-(3-Fluoro-4-[1,2,4]triazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-thioacetamide

The title compound was prepared fromN-[1-(3-fluoro-4-[1,2,4]triazol-1-yl-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]acetamide,obtained in example 25, and Lawesson's reagent by following the similarprocedure as described in example 24.

¹H NMR (CDCl₃+DMSO-d₆): δ 10.41 (bs, 1H), 8.91 (d, J=2.44 Hz, 1H), 8.77(s, 1H), 8.21-7.95 (m, 3H), 7.43 (s, 1H), 4.92 (d, J=4.9 Hz, 2 H), 2.50(s, 3H); MS (m/e): 318 (M⁺+1), 302, 289, 215; IR (KBr, cm⁻¹): 3234,3214, 1532.

EXAMPLE 27{1-[3-Fluoro-4-(4-hydroxymethyl-imidazol-1-yl)-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester

To a DMF solution (5 mL) of[1-(4-Azido-2-fluoro-phenyl)-1H-imidazol-4-yl]-methanol (500 mg, 2.14mmol), obtained in preparation 42, and diisopropylethyl amine (332 mg,12.57 mmol) was added prop-2-ylnyl-thiocarbamic acid O-methyl ester (332mg, 2.57 mmol) followed by the addition of cuprous iodide (815 mg, 4.28mmol) in portion and stirred at room temperature for 0.5 hours.Saturated solution of ammonium chloride (10 mL) was added to thereaction mixture followed by the addition of few drops of ammoniumhydroxide solution. The blue colour solution was diluted with ethylacetate (100 mL) and aqueous layer was separated. The organic layer waswashed with water followed by brine and dried over sodium sulfate.Evaporation of volatiles on rotavapor and purification of the resultingresidue through silica gel column yielded the white color compound (300mg, 40%). Mp. 179° C.

¹H NMR (DMSO-d₆): δ 9.71 (bs, 1H), 8.83 & 8.79 (2s, 1H, rotamers in aratio of 4:1), 8.18 (d, J=11.8 Hz, 1H), 8.00 (s, 1H), 7.89-7.80 (m, 2H),7.46 (s, 1H), 5.04 (bs, 1H), 4.75 (d, J=5.6 Hz, 2H), 4.43 (d, J=5.4 Hz,2H), 3.95 & 3.89 (2s, 3H, rotamers in a ratio of 1:4); MS (m/e): 363(M⁺+1), 331; IR (KBr, cm⁻¹): 3427, 2925, 2854, 2689, 1536.

EXAMPLE 28{1-[3,5-Difluoro-4-(4-hydroxymethyl-imidazol-1-yl)-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester

The title compound was prepared, by following a same procedure reportedfor the preparation of example 27, starting from the3,4,5-trifluoronitrobenzene.

¹H NMR (CDCl₃+DMSO-d₆): δ 9.73 (bs, 1H), 8.88 & 8.83 (2s, 1H, rotamersin a ratio of 4:1), 8.11 (d, J=8.8 Hz, 1H), 7.93 (s, 1H), 7.34 (s, 1H),5.05 (t, J=5.6 Hz, 1H), 4.77 (d, J=5.4 Hz, 2H), 4.30 (d, J=5.6 Hz, 2H),3.89 & 3.33 (2s, 3H, rotamers in a ratio of 1:4). MS (m/e): 381(M⁺+1),349, 192; IR (KBr, cm⁻¹): 3446, 1537.

EXAMPLE 29{1-[4-(4-Cyano-imidazol-1-yl)-3-fluoro-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-thiocarbamicacid O-methyl ester

The title compound was prepared from1-(4-azido-2-fluoro-phenyl)-1H-imidazole-4-carbonitrile (230 mg, 1.0mmol) following the procedure described in example 10 (yield, 150 mg,40%).

IR (KBr, cm⁻¹): 3327, 3127, 2925, 2238, 1538.

¹H NMR (DMSO-d₆): δ 9.71 (bs, 1H), 8.86 & 8.82 (2s, in a ratio of 4:1,1H), 8.67 (s, 1H), 8.39 (s, 1H), 8.25 (d, J=11.5 Hz, 1H), 7.90-8.10 (m,2H), 4.76 & 4.50 7.43 (2d, rotamers in a ratio of 4:1, J=5.6 Hz, 1H),3.95 & 3.89 (2s, rotamers in a ratio of 1:4, 3H).

MS (m/e): 358 (M⁺+1), 326, 269.

EXAMPLE 30{1-[4-(4-Cyano-imidazol-1-yl)-3,5-difluoro-phenyl]-1H-[1,2,3]triazol-4ylmethyl}-thiocarbamicacid O-methyl ester

This compound was prepared by following the procedure as described inExample 10.

IR (KBr, cm−1): 3369, 2242, 1531.

¹H NMR (DMSO-d₆): δ 9.74 (bs, 1H), 8.90 & 8.85 (2s, rotamers in a ratioof 4:1, 1H), 8.62 (s, 1H), 8.35 (s, 1H), 8.19 (d, J=8.9 Hz, 2H), 4.76 &4.47 (2d, rotamers in a ratio 6f 4:1, J=5.6 Hz, 2H), 3.95 & 3.89 (2s,rotamers in a ratio of 1:4, 3H).

MS (m/e): 376 (M⁺+1), 344, 257.

In Vitro Data

Minimum Inhibiton Concentrations (MICs) were determined by brothmicrodilution technique as per the guidelines prescribed in the fifthedition of Approved Standards, NCCLS document M7-A5 Vol 20-No 2, 2000Villinova, Pa.

Initial stock solution of the test compound was prepared in DMSO.Subsequent two fold dilutions were carried out in sterile Mueller HintonBroth (Difco) (MHB).

Frozen cultures stocks were inoculated into 50 ml sterile MHB in 250 mlErlyn Meyer flasks.

-   Composition of MHB is as follows:-   Beef Extract Powder—2.0 grams/litre-   Acid Digest of Casein—17.5 grams/litre-   Soluble Starch—1.5 grams/litre-   Final pH 7.3±0.1

Flasks were incubated for 4 to 5 hours at 35° C. on a rotary shaker at150 rpm. Inoculum was prepared by diluting the culture in sterile MHB toobtain a turbidity of 0.5 McFarland standard. This corresponds to1-2×10⁸ CFU/ml. The stock was further diluted in sterile broth to obtain1-2×10⁶ CFU/ml. 50 μl of the above diluted inoculum was added from 1-10wells. The plates were incubated overnight at 37° C.

MIC is read as the lowest concentration of the compound that completelyinhibits growth of the organism in the microdilution wells as detectedby the unaided eye. Organism Culture No. DRCC No. Staphylococcus aureusATCC 33591 019 Staphylococcus aureus ATCC 49951 213 Staphylococcusaureus ATCC 29213 035 Enterococcus faecalis ATCC 29212 034 Enterococcusfaecalis NCTC 12201 153 Enterococcus faecium NCTC 12202 154 Escherichiacoli ATCC 25922 018 Haemophilus influenzae ATCC 49247 432 Haemophilusinfluenzae ATCC 49766 433 Haemophilus influenzae ATCC 9006 529 Moraxellacatarrhalis ATCC 25238 300 Streptococcus pneumoniae ATCC 6303 236Streptococcus pneumoniae ATCC 49619 237 Streptococcus pneumoniae ATCC700673 238 S. aureus - MRSA — 446 S. aureus - MRSA — 448 S. aureus -MRSA — 449 Corynebacterium jeikeium Viridans Streptococci

-   ATCC: American Type Culture Collection, USA-   NCTC: National Collections of Type Cultures, Colindale, UK-   DRCC: Dr. Reddy's Culture Collection, Hyderabad, India.

The in vitro antibacterial activity data is shown in TABLE 1. TABLE 1 Invitro Activity of Compounds against Gram positive and Gram negativebacteria Antimicrobial Screening (MIC) μg/mL Staphylococcus Ex- aureusam- 213 Enterococcus sp Myco- Salmo- ple 019 Smith 035 034 153 154bacterium nella No. MRSA S S S R R MTCC006 TA97 8 0.5 0.5 1 0.5 0.5 0.532 32 9 1 1 1 2 1 2 4 32 20 8 16 16 32 32 32 16 32 27 1 1 1 2 1 2 16 32

1. A compound of formula (I)

where R¹ represents halogen, azido, thioalcohol, isothiocyanate,hydroxy, isoindole-1,3-dione, substituted or unsubstituted(C1-C20)alkylsulfonyloxy, arylsulfonyloxy, (C1-C20)acyloxy group, NHR⁴where R⁴ represents hydrogen, substituted or unsubstituted groupsselected from (C1-C20)alkyl, (C1-C20)acyl, thio(C1-C20)acyl,(C1-C20)alkoxycarbonyl, (C3-C20)cycloalkoxycarbonyl,(C3-C20)cycloalkoxythiocarbonyl, (C2-C20)alkenyloxycarbonyl,(C2-C20)alkenylcarbonyl, heteroaryl, aryloxycarbonyl,heteroarylcarbonyl, heteroarylthiocarbonyl, (C1-C20)alkoxythiocarbonyl,(C2-C20)alkenyloxythiocarbonyl, aryloxythiocarbonyl,—C(═O)—C(═O)—(C1-C20)alkyl, —C(═O)—C(═O)-aryl,—C((═O)—C(═O)—(C1-C20)alkoxy, —C(═O)—C(═O)-aryloxy,—C(═O)—C(═S)—(C1-C20)alkyl, —C(═O)—C(═S)-aryl, —C(═S)—S—(C1-C20)alkyl,—C(═S)—NH₂, —C(═S)—NH—(C1-C20)alkyl, —C(═S)—N—((C1-C20)alkyl)₂,—C(═S)—NH—(C2-C20)alkenyl, —C(═S)—C(═O)—(C1-C20)alkoxy,—C(═S)—C(═O)-aryloxy, —C(═S)—O—C(═O)—(C1-C20)alkyl,—C(═S)—C(═S)—(C1-C20)alkyl, —C(═S)—C(═S)-aryl, —C(═S)—NH—C(═O)-aryl,—C(═S)—NH-aralkyl, —C(═S)—NH-heteroaralkyl, —C(═NH)—NH₂,—C(═NH)—(C1-C20)alkyl, —C(═NH)-aryl, —S(O)₂(C1-C20)alkyl, —S(O)₂aryl,thiomorpholinylthiocarbonyl, pyrrolidinylthiocarbonyl or —C(═S)—N(R′R″),where R′ and R″ together form a substituted or unsubstituted 5 or 6member heterocycle ring containing nitrogen and optionally having one ortwo additional hetero atoms selected from O or S; R² and R³ may be sameor different and independently represent hydrogen, halogen atom,substituted or unsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl,(C1-C20)alkoxy, aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a)represents substituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y²may be same or different and independently represent hydrogen, halogen,cyano, nitro, formyl, hydroxy, amino, substituted or unsubstitutedgroups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkyl carbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkyl carbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkyl aminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkyl amino, di(C1-C20)alkylamino, arylamino,(C1-C20)alkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl,heterocyclyl, heterocycloalkyl or heteroaralkenylaminoalkyl; or any oneor two of Y¹ or Y² may represent substituted or unsubstituted —CH═NOR′″,wherein R′″ represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl,heteroaryl and aralkyl group, carboxylic acid or its derivatives; A, Band D independently represent N or —CH; their pharmaceuticallyacceptable salts.
 2. The compound of formula (I), as claimed in claim 1,wherein a substituted or unsubstituted 5 or 6 member heterocycle ringformed by R′ & R″, containing nitrogen, optionally having one or twoadditional heteroatoms selected from oxygen, nitrogen or sulfur, isselected from pyrrolidinyl, pyrrolyl, morpholinyl, thiomorpholinyl,benzothiazole, benzoimidazolyl, pyridinyl, pyridazinyl, pyrimidinyl orpyrazinyl.
 3. The compound of formula (I), as claimed in claim 1,wherein the substituents on R⁴, 4^(4a), 4^(4b), 4^(4c), 4^(4d), 4^(4e),R, R⁷ and the heterocycle formed by R′ and R″ are selected from halogenatom, hydroxy, amino, cyano, nitro, (C1-C20)alkyl, hydroxy(C1-C20)alkyl,(C1-C20)alkoxy, ═O, ═S, aryl, hydroxyaryl, pyridyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, (C1-C20)acyl,thio(C1-C20)acyl, (C1-C20)alkoxycarbonyl, (C1-C20)alkoxyaryl orcarboxylic acid or its derivatives.
 4. The compound of formula (I), asclaimed in claim 1, wherein the substituents on R² and R³ are selectedfrom the group consisting of hydroxy, halogen, nitro, amino,(C1-C20)alkyl, (C1-C20)alkoxy, ═O, ═S, cyano group or carboxylic acid orits derivatives.
 5. The compound of formula (I), as claimed in claim 1,wherein the substituents on R^(a) are selected from from hydroxy,halogen, nitro, amino, (C1-C20)alkyl, (C1-C20)alkoxy, cyano group, orcarboxylic acid or its derivatives.
 6. The compound of formula (I), asclaimed in claim 1, wherein the substituents on Y¹ and Y² are selectedfrom hydroxy, nitro, cyano, amino, tert-butyldimethylsilyloxy (TBSO),halogen atom, (C1-C20)alkyl, (C1-C20)alkoxy, (C3-C20)cycloalkyl, aryl,benzyloxy, acyl or acyloxy group.
 7. The compound of formula (I), asclaimed in claim 1, wherein the substituents on R^(c) and R^(d) areselected from halogen, hydroxy, nitro, amino, cyano, (C1-C20)alkyl or(C1-C20) alkoxy.
 8. The compound of formula (I), as claimed in, whereinR¹ represents NHR⁴ where R⁴ represents (C1-C20)acyl,C1-C20)alkoxycarbonyl; R² and R³ may be same or different andindependently represent hydrogen, halogen atom, (C1-C20)alkyl group,halo(C1-C20)alkyl; Y¹ and Y² may be same or different and independentlyrepresent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino,substituted or unsubstituted groups selected from (C1-C20)alkyl,hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkyl carbonyl,(C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl, (C1-C20)alkylsulfonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,amino(C1-C20)allyl, mono(C1-C20)alkylamino, di(C1-C20)alkylamino,(C1-C20)alkoxy, or any one or two of Y¹ or Y² may represent substitutedor unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen and(C1-C20)alkyl group, carboxylic acid or its derivatives.
 9. The compoundof formula (I), as claimed in claim 1, wherein R¹ represents NHR⁴ whereR⁴ represents (C1-C20)acyl, C1-C20)alkoxycarbonyl; R² and R³ may be sameor different and independently represent hydrogen, halogen atom,halo(C1-C20)alkyl; Y¹ and Y² may be same or different and independentlyrepresent hydrogen, cyano, halogen, nitro, formyl, hydroxy, amino,substituted or unsubstituted groups selected from (C1-C20)alkyl,hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkylcarbonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,amino(C1-C20)alkyl, mono(C1-C20)alkylamino, di(C1-C20)alkylamino,(C1-C20)alkoxy, or any one or two of Y¹ or Y² may represent substitutedor unsubstituted —CH═NOH, carboxylic acid or its derivatives. Thesubstituents on Y¹ and Y² may be selected from hydroxy, cyano, amino,(C1-C20)alkyl, (C1-C20)alkoxy, acyl, COOR^(c), wherein R^(c) representshydrogen or (C1-C20)alkyl.
 10. The compound of formula (I), as claimedin claim 1, wherein R¹ represents NHR⁴ where R⁴ representsthio(C1-C20)acyl, (C1-C20)alkoxythiocarbonyl, R² and R³ may be same ordifferent and independently represent hydrogen, halogen atom,(C1-C20)alkyl group, halo(C1-C20)alkyl; Y¹ and Y² may be same ordifferent and independently represent hydrogen, halogen, cyano, nitro,formyl, hydroxy, amino, substituted or unsubstituted groups selectedfrom (C1-C20)alkyl, hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkylcarbonyl,(C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl, (C1-C20)alkylsulfonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,amino(C1-C20)alkyl, mono(C1-C20)alkylamino, di(C1-C20)alkylamino,(C1-C20)alkoxy, or any one or two of Y¹ or Y² may represent substitutedor unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen and(C1-C20)alkyl group, carboxylic acid or its derivatives.
 11. Thecompound of formula (I), as claimed in claim 1, wherein R¹ representsNHR⁴ where R⁴ represents thio(C1-C20)acyl, (C1-C20)alkoxythiocarbonyl,R² and R³ may be same or different and independently represent hydrogen,halogen atom, halo(C1-C20)alkyl; Y¹ and Y² may be same or different andindependently represent hydrogen, cyano, halogen, nitro, formyl,hydroxy, amino, substituted or unsubstituted groups selected from(C1-C20)alkyl, hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkylcarbonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,amino(C1-C20)alkyl, mono(C1-C20)alkylamino, di(C1-C20) alkylamino,(C1-C20)alkoxy, or any one or two of Y¹ or Y² may represent substitutedor unsubstituted —CH═NOH, carboxylic acid or its derivatives. Thesubstituents on Y¹ and Y² may be selected from hydroxy, cyano, amino,(C1-C20)alkyl, (C1-C20)alkoxy, acyl, COOR^(c), wherein R^(c) representshydrogen or (C1-C20)alkyl.
 12. The compound of formula (I), as claimedin claim 1, which is


13. The compound of formula (I), as claimed in claim 1, which is


14. The compound of formula (I), as claimed in claim 1, which is


15. The compound of formula (I), as claimed in claim 1, which is


16. The compound of formula (I), as claimed in claim 1, which is


17. The compound of formula (I), as claimed in claim 1 is


18. The compound of formula (I), as claimed in claim 1 is


19. The compound of formula (I), as claimed in claim 1 is


20. The compound of formula (I), as claimed in claim 1 is


21. The compound of formula (I), as claimed in claim 1 is


22. A preferred compound of the present invention is


23. A process for the preparation of the compound of formula (I)

where R¹ represents azido group; R² and R³ may be same or different andindependently represent hydrogen, halogen atom, substituted orunsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl, (C1-C20)alkoxy,aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a) representssubstituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y² may be sameor different and independently represent hydrogen, halogen, cyano,nitro, formyl, hydroxy, amino, substituted or unsubstituted groupsselected from (C1-C20)alkyl, hydroxy(C1-C20)allyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy,aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl,heterocycloalkyl or heteroaralkenylaminoalkyl; or any one or two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″, wherein R′″represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl andaralkyl group, carboxylic acid or its derivatives; A, B and Dindependently represent N or —CH, which comprises: (a) (i) reacting thecompound of formula (Ia)

where X represents halogen atom; R² and R³ are as defined above, with acompound of formula (Ib)

where A, B, D, Y¹ and Y² are as defined above, to produce a compound offormula (Ic)

where A, B, D, Y¹, Y², R² and R³ are as defined above, (ii) reducing thecompund of formula (Ic) by using reducing agent, to a compound offormula (Id)

where A, B, D, Y¹, Y², R² and R³ are as defined above, (iii) convertingthe compound of formula (Id) to a compound of formula (Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined above, (iv) convertingthe compound of formula (Ie) to a compound of formula (If)

where R^(c) represents substituted or unsubstituted (C1-C20)alkyl group;A, B, D, Y¹, Y², R² and R³ are as defined above, (v) reducing thecompound of formula (If), to give a compound of formula (I)

where R¹ represents hydroxy group; A, B, D, Y¹, Y², R² and R³ are asdefined above, (vi) converting the compound of formula (I), where R¹represents hydroxy group, to a compound of formula (I), where R¹represents substituted or unsubstituted (C1-C20)alkylsulfonyloxy orarylsulfonyloxy group and all other symbols are as defined above, and(vii) converting the compound of formula (I) where R¹ representssubstituted or unsubstituted (C1-C20)alkylsulfonyloxy or arylsulfonyloxygroup, to a compound of formula (I) where R¹ represents azido group andall other symbols are as defined above or (b) (i) reacting the compoundof formula (Ia)

where X represents halogen atom; R² and R³ are as defined earlier, witha compound of formula (II)

where M represents metal atom such as sodium, potassium and the like, toproduce a compound of formula (2m)

where R² and R³ are as defined above, (ii) reducing the compound offormula (Im) by using reducing agent to a compound of formula (In)

where R² and R³ are as defined above, (iii) converting the compound offormula (In) to a compound of formula (Io)

where R² and R³ are as defined above, (iv) reacting the compound offormula (Io), with compound of formula (Ip)

where R¹ is as defined above, to obtain a compound of formula (Iq)

where R¹ represents NHR⁴ wherein R⁴ is as defined above, R² and R³ areas defined above, (v) converting the compound of formula (Iq), to acompound of formula (Ir)

where R¹ is as defined above, R² and R³ are as defined above, (vi)converting the compound of formula (Ir), to a compound of formula (I)

where R¹ is as defined above; R² and R³ are as defined above, (c) (i)converting the compound of formula (Io)

where R² and R³ are as defined above, to a compound of formula (Is)

where R² and R³ are as defined above, (ii) converting the compound offormula (Is), to a compound of formula (Ie)

where all symbols are as defined above and (iii) reacting the compoundof formula (Ie), with a compound of formula (Ip)

where R¹ is as defined in the description, to a compound of formula (I)

where R¹ is as defined above and all other symbols are as defined above.(d) (i) converting the compound of formula (Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined above, to a compound offormula (I)

where R¹ represents hydroxy; A, B, D, Y¹, Y², R² and R³ are as definedabove and (ii) reacting the compound of formula (I) where R¹ representshydroxy group, with MsCl, triethylamine and sodium azide to give acompound of formula (I) where R¹ represents azido group and all othersymbols are as defined above or (e) (i) converting the compound offormula (Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined above, to a compound offormula (I)

where R¹ represents halogen atom and all other symbols are as definedabove and (ii) converting the compound of formula (I) where R¹represents halogen atom, to a compound of formula (I), wherein R¹represents azido group.
 24. A process for the preparation of compound offormula (I)

R¹ represents NHR⁴ wherein R⁴ represents hydrogen atom; R² and R³ may besame or different and independently represent hydrogen, halogen atom,substituted or unsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl,(C1-C20)alkoxy, aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a)represents substituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y²may be same or different and independently represent hydrogen, halogen,cyano, nitro, formyl, hydroxy, amino, substituted or unsubstitutedgroups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy,aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl,heterocycloalkyl or heteroaralkenylaminoalkyl; or any one or two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″, wherein R′″represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl andaralkyl group, carboxylic acid or its derivatives; A, B and Dindependently represent N or —CH, which comprises: (a) (i) convertingthe compound of formula (If)

where R^(c) represents substituted or unsubstituted (C1-C20)alkyl group;A, B, D, Y¹, Y², R² and R³ are as defined above, to a compound offormula (Ig)

where all symbols are as defined above and (ii) reducing the compound offormula (Ig), to produce a compound of formula (I)

where R¹ represents NHR⁴ wherein R⁴ represents hydrogen atom and allother symbols are as defined above or (b) (i) reducing the compound offormula (I) wherein R¹ represents azido group, to produce compound offormula (I)

where R represents NHR⁴ wherein R⁴ represents hydrogen atom; A, B, D,Y¹, Y², R² and R³ are as defined above.
 25. A process for thepreparation of compound of formula (I)

R¹ represents hydroxy group; R² and R³ may be same or different andindependently represent hydrogen, halogen atom, substituted orunsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl, (C1-C20)alkoxy,aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a) representssubstituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y² may be sameor different and independently represent hydrogen, halogen, cyano,nitro, formyl, hydroxy, amino, substituted or unsubstituted groupsselected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, amino(C1-C20)alkyl, mono(C1-C20)alkylamino,di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy, aryl, aryloxy, aralkyl,heteroaryl, heteroaralkyl, heterocyclyl, heterocycloalkyl orheteroaralkenylaminoalkyl; or any one or two of Y¹ or Y² may representsubstituted or unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen,(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl and aralkyl group,carboxylic acid or its derivatives; A, B and D independently represent Nor —CH, which comprises: (a) (i) reacting the compound of formula (Ia)

where X represents halogen atom;. R² and R³ are as defined above, with acompound of formula (Ib)

where A, B, D, Y¹ and Y² are as defined above, to produce a compound offormula (Ic)

where A, B, D, Y¹, Y², R² and R³ are as defined above, (ii) reducing thecompund of formula (Ic) by using reducing agent, to a compound offormula (Id)

where A, B, D, Y¹, Y², R² and R³ are as defined above, (iii) convertingthe compound of formula (Id) to a compound of formula (Ie)

where A, B, D, Y¹, Y², R² and R³ are as defined above, (iv) convertingthe compound of formula (Ie) to a compound of formula (If)

where R^(c) represents substituted or unsubstituted (C1-C20)alkyl group;A, B, D, Y¹, Y², R² and R³ are as defined above, (v) reducing thecompound of formula (If), to give a compound of formula (I)

where R¹ represents hydroxy group; A, B, D, Y¹, Y², R² and R³ are asdefined above, or (b) (i) converting the compound of formula (Ie),

where A, B, D, Y¹, Y², R² and R³ are as defined above, to a compound offormula (I),

where R¹ represents substituted or unsubstituted (C1-C20)acyloxy group,and all other symbols are as defined above and (ii) hydrolysis of thecompound of formula (I) where R¹ represents (C1-C20)acyloxy group, to acompound of formula (I), where R¹ represents hydroxy group and all othersymbols are as defined above.
 26. A process for the preparation ofcompound of formula (I)

where R¹ represents NHR⁴, wherein R⁴ represents substituted orunsubstituted acetyl group; R² and R³ may be same or different andindependently represent hydrogen, halogen atom, substituted orunsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl, (C1-C20)alkoxy,aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a) representssubstituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y² may be sameor different and independently represent hydrogen, halogen, cyano,nitro, formyl, hydroxy, amino, substituted or unsubstituted groupsselected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy,aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl,heterocycloalkyl or heteroaralkenylaminoalkyl; or any one or two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″, wherein R′″represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl andaralkyl group, carboxylic acid or its derivatives; A, B and Dindependently represent N or —CH, which comprises: reacting the compoundof formula (I) where R¹ represents azido group and all other symbols areas defined above, with thiolacetic acid.
 27. A process for thepreparation of compound of formula (I)

where R¹ represents NHR⁴, where R⁴ represents substituted orunsubstituted —C(═S)—R^(4a), wherein R^(4a) represents (C1-C20)alkyl,halo(C1-C20)alkyl, aryl, heteroaryl, —C(═O)—(C1-C20)alkoxy,—C(═O)—(C1-C20)alkoxy, —C(═O)-aryloxy, —C(—S)—(C1-C20)alkyl or—C(═S)-aryl; R² and R³ may be same or different and independentlyrepresent hydrogen, halogen atom, substituted or unsubstituted(C1-C20)alkyl group, halo(C1-C20)allyl, (C1-C20)alkoxy, aryl,heteroaryl, cyano, nitro, OR^(a) where R^(a) represents substituted orunsubstituted (C1-C20)alkyl group; Y¹ and Y² may be same or differentand independently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, substituted or unsubstituted groups selected from(C1-C20)alkyl, hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkylcarbonyl,(C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl, (C1-C20)alkylsulfonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,amino(C1-C20)alkyl, mono(C1-C20)alkylamino, di(C1-C20)alkylamino,arylamino, (C1-C20)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl, heterocycloalkyl orheteroaralkenylaminoalkyl; or any one or two of Y¹ or Y² may representsubstituted or unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen,(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl and aralkyl group,carboxylic acid or its derivatives; A, B and D independently represent Nor —CH, which comprises: reacting the compound of formula (I) where R¹represents NHR⁴, where R⁴ represents substituted or unsubstituted—C(═O)—R^(4a), wherein R^(4a) represents (C1-C20)alkyl,halo(C1-C20)alkyl, aryl, heteroaryl, —C(═O)—(C1-C20)alkoxy,—C(═O)-aryloxy, —C(—S)—(C1-C20)alkyl or —C(═S)-aryl and all othersymbols are as defined above, with a solution of amide and Lawesson'sreagent(2,4-bis(methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide). 28.A process for the preparation of compound of formula (I)

where R¹ represents NHR⁴, wherein R⁴ represents substituted orunsubstituted —C(═S)—OR^(4b), wherein R^(4b) represents (C1-C20)alkyl,cyclo(C3-C20)alkyl, aryl, (C2-C20)alkenyl or —(C═O)—(C1-C20)alkyl group;R² and R³ may be same or different and independently represent hydrogen,halogen atom, substituted or unsubstituted (C1-C20)alkyl group,halo(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl, cyano, nitro,OR^(a) where R^(a) represents substituted or unsubstituted (C1-C20)alkylgroup; Y¹ and Y² may be same or different and independently representhydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, substituted orunsubstituted groups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy,aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl,heterocycloalkyl or heteroaralkenylaminoalkyl; or any one or two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″, wherein R′″represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl andaralkyl group, carboxylic acid or its derivatives; A, B and Dindependently represent N or —CH, which comprises: (i) converting thecompound of formula (I)

where R¹ represents azido group; and all other symbols are as definedabove, to a compound of formula (1), where R¹ represents NHR⁴, whereinR⁴ represents hydrogen atom and all other symbols are as defined above,(ii) converting the compound of formula (I, where R¹ represents NHR⁴,wherein R⁴ represents hydrogen atom, to a compound of formula (I), whereR¹ represents isothiocyanate group; and all symbols are as definedabove, (iii) converting compound of formula (I) where R¹ representsisothiocynate group, to a compound of formula (I), where R¹ representsNHR⁴, wherein R⁴ represents substituted or unsubstituted —C(═S)—OR^(4b),wherein R^(4b) is as defined above and all other symbols are as definedabove.
 29. A process for the preparation of compound of formula (I)

where R¹ represents NHR⁴, where R⁴ represents substituted orunsubstituted groups selected from —C(═S)—NH₂, —C(═S)—NH—(C1-C20)alkyl,—C(═S)—N—((C1-C20)alkyl)₂, —C(═S)—NH—(C2-C20)alkenyl,C(═S)—NH—C(═O)-aryl, —C(═S)—NH-aralkyl, —C(═S)—NH-heteroaralkyl or—C(═S)—N(R′R″), wherein R′ and R″ groups together form a substituted orunsubstituted 5 or 6 membered cyclic ring containing nitrogen andoptionally having one or two additional hetero atoms selected from O orS; R² and R³ may be same or different and independently representhydrogen, halogen atom, substituted or unsubstituted (C1-C20)alkylgroup, halo(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl, cyano,nitro, OR^(a) where R^(a) represents substituted or unsubstituted(C1-C20)alkyl group; Y¹ and Y² may be same or different andindependently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy; amino, carboxyl or substituted or unsubstituted groups selectedfrom (C1-C20)alkyl, hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkylcarbonyl,(C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl, (C1-C20)alkylsulfonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkyl aminocarbonyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,amino(C1-C20)alkyl, mono(C1-C20)alkylamino, di(C1-C20)alkylamino,arylamino, (C1-C20)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl, heterocycloalkyl orheteroaralkenylaminoalkyl; or any one or two of Y¹ or Y² may representsubstituted or unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen,(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl and aralkyl group,carboxylic acid or its derivatives; A, B and D independently represent Nor —CH, which comprises: reacting a compound of formula (I) where R¹represents isothiocyanate group and all other symbols are as definedabove, with ammonia gas or amine.
 30. A process for the preparation ofcompound of formula (I)

where R¹ represents NHR⁴, wherein R⁴ represents substituted orunsubstituted —C(═S)—SR^(4c), wherein R^(4c) represents (C1-C20)alkylgroup; R² and R³ may be same or different and independently representhydrogen, halogen atom, substituted or unsubstituted (C1-C20)alkylgroup, halo(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl, cyano,nitro, OR^(a) where R^(a) represents substituted or unsubstituted(C1-C20)alkyl group; Y¹ and Y² may be same or different andindependently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, carboxyl or substituted or unsubstituted groups selectedfrom (C1-C20)alkyl, hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkylcarbonyl,(C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl, (C1-C20)alkylsulfonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,amino(C1-C20)alkyl, mono(C1-C20)alkylamino, di(C1-C20)alkylamino,arylamino, (C1-C20)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl, heterocycloalkyl orheteroaralkenylaminoalkyl; or any one or two of Y¹ or Y² may representsubstituted or unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen,(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl and aralkyl group,carboxylic acid or its derivatives; A, B and D independently represent Nor —CH, which comprises: reacting the compound of formula (I), where R¹represents NHR⁴, wherein R⁴ represents hydrogen atom and all othersymbols are as defined above, with CS₂ and alkylhalide.
 31. A processfor the preparation of compound of formula (I)

where R¹ represents NHR⁴, wherein R⁴ represents substituted orunsubstituted —C(═S)—NH—R^(4d), wherein R^(4d) represents C(═O)-arylgroup; R² and R³ may be same or different and independently representhydrogen, halogen atom, substituted or unsubstituted (C1-C20)alkylgroup, halo(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl, cyano,nitro, OR^(a) where R^(a) represents substituted or unsubstituted(C1-C20)alkyl group; Y¹ and Y² may be same or different andindependently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, carboxyl or substituted or unsubstituted groups selectedfrom (C1-C20)alkyl, hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkyl carbonyl,(C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl, (C1-C20)alkylsulfonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,amino(C1-C20)alkyl, mono(C1-C20)alkyl amino, di(C1-C20)alkylamino,arylamino, (C1-C20)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl, heterocycloalkyl orheteroaralkenylaminoalkyl; or any one or two of Y¹ or Y² may representsubstituted or unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen,(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl and aralkyl group,carboxylic acid or its derivatives; A, B and D independently represent Nor —CH, which comprises: reacting the compound of formula (I), where R¹represents NHR⁴, wherein R⁴ represents hydrogen atom and all othersymbols are as defined above, with benzoylisothiocyanate.
 32. A processfor the preparation of compound of formula (I)

where R¹ represents NHR⁴, wherein R⁴ represents substituted orunsubstituted group selected from —C(═O)-heteroaryl; R² and R³ may besame or different and independently represent hydrogen, halogen atom,substituted or unsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl,(C1-C20)alkoxy, aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a)represents substituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y²may be same or different and independently represent hydrogen, halogen,cyano, nitro, formyl, hydroxy, amino, carboxyl or substituted orunsubstituted groups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20) (C1-C20)alkylaminocarbonyl,alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy,aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl,heterocycloalkyl or heteroaralkenylaminoalkyl; or any one or two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″, wherein R′″represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl andaralkyl group, carboxylic acid or its derivatives; A, B and Dindependently represent N or —CH; their pharmaceutically acceptablesalts and pharmaceutical compositions containing them, which comprises:reacting the compound of formula (I), where R¹ represents NHR⁴, whereinR⁴ represents hydrogen atom and all other symbols are as defined above,with heteroaryl acid chloride.
 33. A process for the preparation ofcompound of formula (I)

where R¹ represents NHR⁴ where R⁴ represents substituted orunsubstituted —(C═O)—R^(4e) wherein R^(4e) represents (C1-C20)alkyl,(C1-C20)alkoxy, (C2-C20)alkenyl, halo(C1-C20)alkyl, aryl, aryloxy,heteroaryl, (C2-C20)alkenyloxy, (C1-C20)alkylcarbonyl, arylcarbonyl,aryloxycarbonyl, (C1-C20)alkoxycarbonyl, (C1-C20)alkylthiocarbonyl or(C1-C20)arylthiocarbonyl; R² and R³ may be same or different andindependently represent hydrogen, halogen atom, substituted orunsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl, (C1-C20)alkoxy,aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a) representssubstituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y² may be sameor different and independently represent hydrogen, halogen, cyano,nitro, formyl, hydroxy, amino, carboxyl or substituted or unsubstitutedgroups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy,aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl,heterocycloalkyl or heteroaralkenylaminoalkyl; or any one or two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″, wherein R′″represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl andaralkyl group, carboxylic acid or its derivatives; A, B and Dindependently represent N or —CH; their pharmaceutically acceptablesalts and pharmaceutical compositions containing them, which comprises:reacting the compound of formula (I), where R¹ represents NHR⁴, whereinR⁴ represents hydrogen atom and all other symbols are as defined above,with acid halide, alkylchloroformate or anhydride of acid.
 34. A processfor the preparation of compound of formula (I)

where R¹ represents NHR⁴ where R⁴ represents substituted orunsubstituted —C(═NH)—NH₂; R² and R³ may be same or different andindependently represent hydrogen, halogen atom, substituted orunsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl, (C1-C20)alkoxy,aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a) representssubstituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y² may be sameor different and independently represent hydrogen, halogen, cyano,nitro, formyl, hydroxy, amino, carboxyl or substituted or unsubstitutedgroups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkyl carbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy,aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl,heterocycloalkyl or heteroaralkenylaminoalkyl; or any one or two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″, wherein R′″represents hydrogen, (C1-C20)allyl, (C1-C20)alkoxy, aryl, heteroaryl andaralkyl group, carboxylic acid or its derivatives; A, B and Dindependently represent N or —CH, which comprises: (a) reacting acompound of formula (I), where R¹ represents NHR⁴ wherein R⁴ representshydrogen atom and all other symbols are as defined above, withdi-tert-butoxy carbonyl thiourea or (b) reacting the compound of formula(I), where R¹ represents NHR⁴ wherein R⁴ represents substituted orunsubstituted group selected from S(O)₂(C1-C20)alkyl or S(O)₂aryl groupand all other symbols are as defined above, with guanidinehydrochloride.
 35. A process for the preparation of compound of formula(I)

where R¹ represents NHR⁴ where R⁴ represents substituted orunsubstituted group selected from —C(═NH)—(C1-C20)alkyl or —C(═NH)-aryl;R² and R³ may be same or different and independently represent hydrogen,halogen atom, substituted or unsubstituted (C1-C20)alkyl group,halo(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl, cyano, nitro,OR^(a) where R^(a) represents substituted or unsubstituted (C1-C20)alkylgroup; Y¹ and Y² may be same or different and independently representhydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, carboxyl orsubstituted or unsubstituted groups selected from (C1-C20)alkyl,hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkylcarbonyl,(C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl, (C1-C20)alkyl sulfonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,amino(C1-C20)alkyl, mono(C1-C20)alkylamino, di(C1-C20)alkylamino,arylamino, (C1-C20)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl, heterocycloalkyl orheteroaralkenylaminoalkyl; or any one or two of Y¹ or Y² may representsubstituted or unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen,(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl and aralkyl group,carboxylic acid or its derivatives; A, B and D independently represent Nor —CH, which comprises: (i) reacting the compound of formula (I)

where R¹ repersents NHR⁴, wherein R⁴ represents —C(═S)—NH₂ and all othersymbols are as defined above, with di tert-butoxy carbonyl ether[(BOC)₂O], to produce a compound of formula (I), where R¹ representsNHR⁴, wherein R⁴ represents —C(═S)—NH₂ group substituted withtert-butoxy carbonyl group and all other symbols are as defined aboveand (ii) reacting the above compound of formula (I), with a compound offormula (Ih)R⁷—NH₂   (Ih) where R⁷ represents substituted or unsubstituted(C1-C20)alkyl or aryl group, to produce a compound of formula (I) whereR¹ represents NHR⁴ where R⁴ represents substituted or unsubstitutedgroup selected from —C(—NH)—(C1-C20)alkyl or —C(═NH)-aryl group and allother symbols are as defined above.
 36. A process for the preparation ofcompound of formula (I)

where R¹ represents halogen atom; R² and R³ may be same or different andindependently represent hydrogen, halogen atom, substituted orunsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl, (C1-C20)alkoxy,aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a) representssubstituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y² may be sameor different and independently represent hydrogen, halogen, cyano,nitro, formyl, hydroxy, amino, carboxyl or substituted or unsubstitutedgroups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkyl sulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkyl amino, arylamino,(C1-C20)alkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl,heterocyclyl, heterocycloalkyl or heteroaralkenylaminoalkyl; or any oneor two of Y¹ or Y² may represent substituted or unsubstituted —CH═NOR′″,wherein R′″ represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl,heteroaryl and aralkyl group, carboxylic acid or its derivatives; A, Band D independently represent N or —CH, which comprises: reacting thecompound of formula (I) where R¹ represents hydroxy group and all othersymbols are as defined above, with SOCl₂, PCl₅/PBr₃, tetrahalomethane,in the presence of PPh₃ or P(alkyl)₃.
 37. A process for the preparationof compound of formula (I)

where R¹ represents ‘SH’ group; R² and R³ may be same or different andindependently represent hydrogen, halogen atom, substituted orunsubstituted (C1-C20)alkyl group, halo(C1-C20)alkyl, (C1-C20)alkoxy,aryl, heteroaryl, cyano, nitro, OR^(a) where R^(a) representssubstituted or unsubstituted (C1-C20)alkyl group; Y¹ and Y² may be sameor different and independently represent hydrogen, halogen, cyano,nitro, formyl, hydroxy, amino, carboxyl or substituted or unsubstitutedgroups selected from (C1-C20)alkyl, hydroxy(C1-C20)alkyl,dihydroxy(C1-C20)alkyl, (C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl,(C1-C20)alkylcarbonyl, (C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl,(C1-C20)alkylsulfonyl, (C1-C20)alkylcarbonylamino(C1-C20)alkyl,arylcarbonylamino(C1-C20)alkyl, (C1-C20)alkylaminocarbonyl,(C1-C20)alkylcarbonyloxy(C1-C20)alkyl, amino(C1-C20)alkyl,mono(C1-C20)alkylamino, di(C1-C20)alkylamino, arylamino, (C1-C20)alkoxy,aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl,heterocycloalkyl or heteroaralkenylaminoalkyl; or any one or two of Y¹or Y² may represent substituted or unsubstituted —CH═NOR′″, wherein R′″represents hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl andaralkyl group, carboxylic acid or its derivatives; A, B and Dindependently represent N or —CH, which comprises: (i) reacting thecompound of formula (I) where R¹ represents halogen atom, to produce acompound of formula (Ii),

where all other symbols are as defined above, with a base andthiolacetic acid, (ii) reacting the compound of formula (Ii), to producea compound of formula (I) where R¹ represents ‘SH’ group and all othersymbols are as defined above, with base.
 38. A process for thepreparation of compound of formula (I)

where R¹ represents NHR⁴, wherein R⁴ represents —S(O)₂(C1-C20)alkyl,—S(O)₂aryl group; R² and R³ may be same or different and independentlyrepresent hydrogen, halogen atom, substituted or unsubstituted(C1-C20)alkyl group, halo(C1-C20)alkyl, (C1-C20)alkoxy, aryl,heteroaryl, cyano, nitro, OR^(a) where R^(a) represents substituted orunsubstituted (C1-C20)alkyl group; Y¹ and Y² may be same or differentand independently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, carboxyl or substituted or unsubstituted groups selectedfrom (C1-C20)alkyl, hydroxy(C1-C20)alkyl, dihydroxy(C1-C20)alkyl,(C1-C20)alkoxy(C1-C20)alkyl, aminocarbonyl, (C1-C20)alkylcarbonyl,(C1-C20)alkoxycarbonyl, carboxy(C1-C20)alkyl, (C1-C20)alkylsulfonyl,(C1-C20)alkylcarbonylamino(C1-C20)alkyl, arylcarbonylamino(C1-C20)alkyl,(C1-C20)alkylaminocarbonyl, (C1-C20)alkylcarbonyloxy(C1-C20)alkyl,amino(C1-C20)alkyl, mono(C1-C20)alkylamino, di(C1-C20)alkylamino,arylamino, (C1-C20)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl, heterocycloalkyl orheteroaralkenylaminoalkyl; or any one or two of Y¹ or Y² may representsubstituted or unsubstituted —CH═NOR′″, wherein R′″ represents hydrogen,(C1-C20)alkyl, (C1-C20)alkoxy, aryl, heteroaryl and aralkyl group,carboxylic acid or its derivatives; A, B and D independently represent Nor —CH, which comprises: reacting the compound of formula (I), where R¹represents NHR⁴ wherein R⁴ represents hydrogen atom.
 39. Apharmaceutical composition comprising a compound of formula (I)

as claimed in claim 1 and a pharmaceutically acceptable carrier,diluent, excipient or solvate.
 40. The pharmaceutical composition asclaimed in claim 39, in the form of a tablet, capsule, powder, syrup,solution or suspension.
 41. A method of treating or preventing abacterial infection comprising administering a therapeutically effectiveamount of a compound of formula (I) as claimed in claim 1 to a patientin need thereof.
 42. A method of treating or preventing a bacterialinfection comprising administering a therapeutically effective amount ofa pharmaceutical composition as claimed in claim 39 or 40, to a patientin need thereof.
 43. A composition comprising a compound as claimed inclaim 12 and a pharmaceutically acceptable carrier, diluent, excipientor solvate.
 44. The pharmaceutical composition as claimed in claim 43,in the form of a tablet, capsule, powder, syrup, solution or suspension.45. A method of treating or preventing a bacterial infection comprisingadministering a therapeutically effective amount of a compound asclaimed in claim 12 to a patient in need thereof.
 46. A method oftreating or preventing a bacterial infection comprising administering atherapeutically effective amount of a composition as claimed in claim 43or 44 to a patient in need thereof.